Pyrazole derivatives

ABSTRACT

The object of the present invention is to provide a novel pyrazole derivative which shows high selectivity to corn, wheat and barley and which is capable of controlling gramineous weeds and broad-leaved weeds together at a low dosage. 
     The pyrazole derivative of the present invention to achieve the above object is the compound of the general formula (I), ##STR1## wherein R 1  is a C 1  -C 6  alkyl group, 
     each of R 2 , R 3 , R 4  and R 5  is independently hydrogen or a C 1  -C 4  alkyl group, 
     R 6  is a C 1  -C 4  alkyl group, 
     R 7  is hydrogen or a C 1  -C 4  alkyl group, 
     X 1  is a C 1  -C 4  alkyl group or a halogen atom, 
     n is an integer of 1 to 3, 
     p 1  is an integer of 0 to 2, and 
     Q 1  is hydrogen, --SO 2  --R 8  or ##STR2## in which R 8  is a C 1  -C 6  alkyl group, 
     Y is hydrogen, a C 1  -C 4  alkyl group or a halogen atom, and 
     m 1  is an integer of 1 to 3.

TECHNICAL FIELD

The present invention relates to pyrazole derivatives. More specifically, it relates to novel pyrazole derivatives, a process for the production thereof, herbicides containing them as active ingredients, and novel intermediate compounds suitable for the production thereof.

TECHNICAL BACKGROUND

During a growing period of corn, etc., a triazine-based herbicide such as atrazine and acid anilide-based herbicides such as alachlor and metolachlor have been conventionally used, while atrazine shows low efficacy to gramineous weeds, and arachlor and metolachlor show low efficacy to broad-leaved weeds. It is therefore difficult at present to control gramineous weeds and broad-leaved weeds at the same time with a single herbicide. Further, the above herbicides are undesirable in view of an environmental problem due to their high dosage requirement.

On the other hand, it is known that specific 4-benzoyl-pyrazole derivatives have herbicidal activity (see JP-A-65-122672, JP-A-63-122673, JP-A-63-170365, JP-A-1-52759, JP-A-2-173 and JP-A-2-288866). Further, for example, pyrazolate of the following formula is known as a commercial herbicide. ##STR3##

However, pyrazole derivatives having a thiochroman ring such as compounds of the present invention have not yet been known so far.

Further, the commercially available herbicide, pyrazolate, is for use in a paddy field, and it hardly has herbicidal activity when used in a plowed field. Further, 4-benzoyl-pyrazole derivatives that have been already disclosed are insufficient in practical use although they have herbicidal activity in a plowed field. For example, the 4-benzoyl-pyrazole derivatives disclosed in JP-A-63-122672 have activity to broad-leaved weeds such as cocklebur, velvetleaf, slender amaranth, etc., when used for foliar treatment, while the activity thereof is practically insufficient. Further, they show very poor activity to gramineous weeds such as green foxtail, large crabgrass, barnyardgrass, etc. In soil treatment, the above derivatives show activity to gramineous weeds such as green foxtail, large crabgrass, barnyardgrass, etc., while they show very poor activity to broad-leaved weeds such as cocklebur, velvetleaf, slender amaranth, etc.

DISCLOSURE OF THE INVENTION

It is an object of the present invention, in a broad sense, to provide a novel pyrazole derivative which shows high selectivity to corn, wheat and barley and which can control gramineous weeds and broad-leaved weeds at low dosage by any one of foliar treatment and soil treatment. More specifically, it is an object of the present invention to provide the above novel pyrazole derivative, a process for the production thereof, a herbicide containing the same as an active ingredient, and a novel intermediate compound suitable for the production thereof.

The novel pyrazole derivative of the present invention is a compound of the general formula (I). ##STR4##

PREFERRED EMBODIMENTS FOR WORKING THE INVENTION

In the general formula (I) for the novel pyrazole derivative of the present invention, R¹ is a C₁ -C₆ alkyl group such as methyl, ethyl, propyl, butyl, pentyl or hexyl, and each of the propyl, butyl, pentyl and hexyl may be linear or branched. R¹ is preferably a C₁ -C₄ alkyl group, more preferably methyl, ethyl or i-propyl.

Each of R², R³, R⁴ and R⁵ is independently hydrogen or a C₁ -C₄ alkyl group. The C₁ -C₄ alkyl includes methyl, ethyl, propyl and butyl, and the propyl and butyl may be linear or branched. Each of R², R³, R⁴ and R⁵ is preferably hydrogen or methyl, more preferably hydrogen.

R⁶ is a C₁ -C₄ alkyl group, and specific examples thereof include those described concerning the above R². R⁶ is preferably methyl or ethyl.

R⁷ is hydrogen or a C₁ -C₄ alkyl group, and the C₁ -C₄ alkyl group includes those described concerning the above R². R⁷ is preferably hydrogen or methyl.

X¹ is a C₁ -C₄ alkyl group or a halogen atom, and the former C₁ -C₄ alkyl group includes those described concerning the above R². The latter halogen atom includes chlorine, bromine, iodine and Fluorine. X¹ is preferably a C₁ -C₄ alkyl group, more preferably methyl.

n is a number of X¹, and it is an integer of 1 to 3. When n is 2 or 3, a plurality of X¹ s may be the same as, or different from, each other. Preferably, n is 1 or 2, and preferably, X¹ is substituted on the 5-position or X¹ s are substituted on the 5-position and 8-position.

p¹ is a number of oxygen atom(s) bonding to the sulfur atom, and it is an integer of 0 to 2. When p¹ =0, sulfide is represented. When p¹ =1, sulfoxide is represented. When p¹ =2, sulfone is represented. p¹ is preferably 1 (sulfoxide) or 2 (sulfone), more preferably 2 (sulfone).

Q¹ is hydrogen, --SO₂ --R⁸ or ##STR5## In the former sulfonyl group, --SO₂ --R⁸, R⁸ is a C₁ -C₆ alkyl group, and specific examples thereof include those described concerning the above R¹. R⁸ is preferably ethyl, n-propyl or i-propyl. In the latter sulfonyl group, ##STR6## Y is hydrogen, a C₁ -C₄ alkyl group or a halogen atom. The C₁ -C₄ alkyl group includes those described concerning the above R² and the halogen atom includes those described concerning the above X¹. m¹ is a number of Y and it is an integer of 1 to 3. When m¹ is 2 or 3, a plurality of Ys may be the same as, or different from, each other. Preferably, m¹ is 1 or 2.

Specific examples of the pyrazole derivative of the general formula (I) are preferably as follows.

                                      TABLE 1                                      __________________________________________________________________________     Structural formula     Name                                                    __________________________________________________________________________      ##STR7##                                                                                              ##STR8##                                                ##STR9##                                                                                              ##STR10##                                               ##STR11##                                                                                             ##STR12##                                               ##STR13##                                                                                             ##STR14##                                               ##STR15##                                                                                             ##STR16##                                               ##STR17##                                                                                             ##STR18##                                               ##STR19##                                                                                             ##STR20##                                               ##STR21##                                                                                             ##STR22##                                               ##STR23##                                                                                             ##STR24##                                               ##STR25##                                                                                             ##STR26##                                               ##STR27##                                                                                             ##STR28##                                               ##STR29##                                                                                             ##STR30##                                               ##STR31##                                                                                             ##STR32##                                               ##STR33##                                                                                             ##STR34##                                               ##STR35##                                                                                             ##STR36##                                               ##STR37##                                                                                             ##STR38##                                               ##STR39##                                                                                             ##STR40##                                               ##STR41##                                                                                             ##STR42##                                               ##STR43##                                                                                             ##STR44##                                               ##STR45##                                                                                             ##STR46##                                               ##STR47##                                                                                             ##STR48##                                               ##STR49##                                                                                             ##STR50##                                               ##STR51##                                                                                             ##STR52##                                               ##STR53##                                                                                             ##STR54##                                               ##STR55##                                                                                             ##STR56##                                               ##STR57##                                                                                             ##STR58##                                               ##STR59##                                                                                             ##STR60##                                               ##STR61##                                                                                             ##STR62##                                               ##STR63##                                                                                             ##STR64##                                               ##STR65##                                                                                             ##STR66##                                               ##STR67##                                                                                             ##STR68##                                               ##STR69##                                                                                             ##STR70##                                               ##STR71##                                                                                             ##STR72##                                               ##STR73##                                                                                             ##STR74##                                               ##STR75##                                                                                             ##STR76##                                               ##STR77##                                                                                             ##STR78##                                               ##STR79##                                                                                             ##STR80##                                               ##STR81##                                                                                             ##STR82##                                               ##STR83##                                                                                             ##STR84##                                               ##STR85##                                                                                             ##STR86##                                               ##STR87##                                                                                             ##STR88##                                               ##STR89##                                                                                             ##STR90##                                               ##STR91##                                                                                             ##STR92##                                               ##STR93##                                                                                             ##STR94##                                               ##STR95##                                                                                             ##STR96##                                               ##STR97##                                                                                             ##STR98##                                               ##STR99##                                                                                             ##STR100##                                              ##STR101##                                                                                            ##STR102##                                              ##STR103##                                                                                            ##STR104##                                              ##STR105##                                                                                            ##STR106##                                              ##STR107##                                                                                            ##STR108##                                              ##STR109##                                                                                            ##STR110##                                              ##STR111##                                                                                            ##STR112##                                              ##STR113##                                                                                            ##STR114##                                              ##STR115##                                                                                            ##STR116##                                              ##STR117##                                                                                            ##STR118##                                              ##STR119##                                                                                            ##STR120##                                              ##STR121##                                                                                            ##STR122##                                              ##STR123##                                                                                            ##STR124##                                              ##STR125##                                                                                            ##STR126##                                              ##STR127##                                                                                            ##STR128##                                              ##STR129##                                                                                            ##STR130##                                              ##STR131##                                                                                            ##STR132##                                              ##STR133##                                                                                            ##STR134##                                              ##STR135##                                                                                            ##STR136##                                              ##STR137##                                                                                            ##STR138##                                              ##STR139##                                                                                            ##STR140##                                              ##STR141##                                                                                            ##STR142##                                              ##STR143##                                                                                            ##STR144##                                              ##STR145##                                                                                            ##STR146##                                              ##STR147##                                                                                            ##STR148##                                              ##STR149##                                                                                            ##STR150##                                              ##STR151##                                                                                            ##STR152##                                              ##STR153##                                                                                            ##STR154##                                              ##STR155##                                                                                            ##STR156##                                             __________________________________________________________________________

The pyrazole derivative of the general formula (I) contains some asymmetric carbon atoms, and includes a variety of isomers. The pyrazole off the present invention includes all of these isomers and isomer mixtures of these.

The pyrazole derivative of the general formula (I) in which Q¹ is hydrogen, i.e., the pyrazole derivative of the formula (Ia) to be described later, can have the following three structures due to its tautomerism. The pyrazole derivative of the present invention includes all of compounds having these structures. ##STR157##

Further, the pyrazole derivative of the general formula (Ia) is an acidic substance, and can be easily converted to a salt by treating it with a base. This salt is also included in the pyrazole derivative of the present invention.

The above base is selected from known bases without any limitation, and examples thereof include organic bases such as amines and anilines and inorganic bases such as sodium salts and potassium salts.

The amines include alkylamine, dialkylamine and trialkylamine. The alkyl group thereof is generally a C₁ -C₄ alkyl group. The anilines include aniline, alkylaniline and dialkylaniline. The alkyl group thereof is generally a C₁ -C₄ alkyl group.

The sodium salts include sodium hydroxide and sodium carbonate. The potassium salts include potassium hydroxide and potassium carbonate.

The pyrazole derivative of the general formula (I) can be produced by any one of three processes provided by the present invention. These processes will be explained one by one hereinafter.

The first process comprises reacting a compound of the general formula (II), ##STR158## [wherein R¹, R², R³, R⁴, R⁵, X¹, n and p¹ are as defined in the general Formula (I)], with a compound of the general formula (III), ##STR159## [wherein R⁶ and R⁷ are as defined in the general formula (I)], to form a pyrazole derivative of the general formula (Ia), ##STR160## [wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X¹, n and p¹ are as defined in the above general formulae (II) and (III)], and optionally reacting the above pyrazole derivative (Ia) with a sulfonic acid halide of the general formula (IV),

    Q.sup.2 X.sup.2                                            (IV)

[wherein Q² is --SO₂ --R⁸ or ##STR161## in which R⁸ is a C₁ -C₆ alkyl group, Y is hydrogen, a C₁ -C₄ alkyl group or a halogen atom, and

m¹ is an integer of 1 to 3, and

X² is a halogen atom],

to obtain a pyrazole derivative of the general formula (Ib), ##STR162## [wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X¹, n, p¹ Q², R⁸, Y and m¹ are as defined in the above general formulae (II). (III) and (IV)].

For making it easier to understand the first process above, the reaction scheme of the first process will be described below. ##STR163##

In the step (1), the compound of the general formula (II) and the compound of the general formula (III) are allowed to react, for example, in the presence of N,N'-dicyclohexylcarbodiimide (to be abbreviated as DCC hereinafter) and a base in an inert solvent to obtain a pyrazole derivative of the general formula (Ia). The pyrazole derivative of the general formula (Ia) obtained in the above step is included in the pyrazole derivative of the general formula (I), provided by the present invention, (that is, the pyrazole derivative of the general formula (Ia) corresponds to the pyrazole derivative of the general formula (I) in which Q¹ is hydrogen).

In the above step (1), the molar ratio of the compound of the general formula (II) to the compound of the general formula (III) is preferably 1:1 to 1:3. DCC is used in an amount of 1.0 to 1.5 mol per mole of the compound of the general formula (II) and the compound of the general formula (III). The base used together with DCC is not specially limited, while it is preferred to use potassium carbonate or sodium carbonate in an amount of 0.5 to 2.0 mol per mole of the compound of the general formula (II) and the compound of the general formula (III). The inert solvent is not specially limited, either, if it is inert to the reaction. However, it is preferably selected From tert-butyl alcohol, tert-amyl alcohol and i-propyl alcohol. The reaction temperature may be from room temperature to the boiling point of the solvent, while it is preferably from approximately 50° to 100° C.

In the step (2), the pyrazole derivative of the general formula (Ia) obtained in the step (1) and the sulfonic acid halide of the general formula (IV) are allowed to react in an inert solvent to obtain a pyrazole derivative of the general formula (Ib). The pyrazole derivative of the general formula (Ib) obtained in this step (2) is also included in the pyrazole derivative of the general formula (I) (that is, the pyrazole derivative of the general formula (Ib) corresponds to the pyrazole derivative of the general formula (I) in which Q¹ is --SO₂ --R⁸ or ##STR164##

In the above step (2), the molar ratio of the compound of the general formula (Ia) to the compound of the general formula (IV) is preferably 1:1 to 1:10. The inert solvent is not specially limited if it is inert to the reaction, while it is preferably selected, for example, from ethers such as diethyl ether and tetrahydrofuran and halogenated hydrocarbons such as dichloromethane and chloroform. In the above step (2), the reaction is preferably carried out in the presence of a base such as sodium carbonate, potassium carbonate, triethylamine or pyridine generally at a temperature of from room temperature to the boiling point of the solvent. Further, the reaction may be carried out in a two-phase solvent system such as water-benzene, water-toluene, water-chloroform or water-dichloromethane. In this case, the reaction proceeds more smoothly when a phase transfer catalyst such as crown ether or benzyltriethylammonium chloride is added to the reaction system.

The pyrazole derivative of the general formula (I) can be also produced by a second process to be detailed below.

The second process comprises reacting a compound of the general formula (II), ##STR165## [wherein R¹, R², R³, R⁴, R⁵, X¹, n and p¹ are as defined in the general formula (I)], with a halogenation agent to form a compound of the general formula (V), ##STR166## [wherein R¹, R², R³, R⁴, R⁵, X¹, n and p¹ are as defined in the general formula (I) and X³ is a halogen atom], then reacting the above compound (V) with a compound of the general formula (III), ##STR167## [wherein R⁶ and R⁷ are as defined in the general formula (I)] to form a compound of the general Formula (VI), ##STR168## [wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X¹, n and p¹ are as defined in the general formula (I)], then heating the above compound (VI) to form a pyrazole derivative of the general formula (Ia), ##STR169##

]wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X¹, n and p¹ are as defined in the general formula (I)], and optionally reacting the above pyrazole derivative (Ia) with a sulfonic acid halide of the general formula (IV),

    Q.sup.2 X.sup.2                                            (IV)

[wherein Q² is --SO₂ --R⁸ or ##STR170## in which R⁸ is a C₁ -C₆ alkyl group, Y is hydrogen, a C₁ -C₄ alkyl group or a halogen atom, and

m¹ is an integer of 1 to 3, and

X² is a halogen atom],

to obtain a pyrazole derivative of the general Formula (Ib), ##STR171## [wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X¹, n p¹, Q², R⁸, Y and m¹ are as defined in the above general formulae (II), (Ill) and (IV)].

For making it easier to understand the second process above, the reaction scheme of the second process will be described below. ##STR172##

In the step (a), the compound of the general formula (II) is allowed to react with a halogenation agent (thionyl chloride or phosphorus oxychloride) to form a compound of the general formula (V). The above step (a) is preferably carried out in the presence of a halogenation agent in an amount greater than the equimolar amount of the compound of the general formula (II). This reaction may be carried out in a diluted state in the presence of an inert solvent (methylene chloride or chloroform), or may be carried out in the absence of a solvent. Further, the reaction may be carried out using, as a solvent, an excess amount of thionyl chloride which is a halogenation agent. Although not specially limited, the reaction temperature is preferably from 0° C. to the boiling point of the solvent, particularly preferably 60° C. or around 60° C.

In the step (b), the compound of the general formula (V) obtained in the step (a) is allowed to react with the compound of the general formula (III) to form the compound of the general formula (VI). The step (b) is preferably carried out with a molar ratio of the compound of the general formula (V) to the compound of the general formula (III) at 1:1 to 1:3 in a solvent inert to the reaction such as dioxane, acetonitrile, benzene, toluene, chloroform, methylene chloride or 1,2-dichloroethane. Further, the reaction may be carried out in a two-phase solvent system such as water-benzene, water-toluene, water-chloroform or water-dichloromethane. The reaction smoothly proceeds in the co-presence of a base such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, triethylamine or pyridine. The reaction temperature is preferably between 0° C. and 60° C., generally room temperature.

In the step (c), the compound of the general formula (VI) obtained in the step (b) is heated to obtain the pyrazole derivative of the general formula (Ia). The pyrazole derivative of the general formula (Ia) obtained in this step (c) is included in the pyrazole derivative of the general formula (I) (that is, the pyrazole derivative of the general formula (Ia) corresponds to the pyrazole derivative of the general formula (I) in which Q¹ is hydrogen).

In the step (c), it is preferred to heat the compound of the general formula (VI) in the presence of a proper base (sodium carbonate, potassium carbonate or triethylamine). The amount of the base is at least an equimolar amount to the compound of the general formula (VI), while it is generally preferably 1.5 mol per mole of the compound of the general formula (VI). The heating temperature is preferably 80° to 150° C. A solvent is not particularly required, while a solvent (dioxane or acetonitrile) inert to the reaction may be used.

The step (d) is the same as the step (2) in the first process described already. In the step (d), the pyrazole derivative of the general formula (Ia) obtained in the step (c) and the sulfonic acid halide of the general formula (IV) are allowed to react in an inert solvent to obtain the pyrazole derivative of the general formula (Ib). The pyrazole derivative of the general formula (Ib) obtained in this step (d) is also included in the pyrazole derivative of the general formula (I) (that is, the pyrazole derivative of the general formula (Ib) corresponds to the pyrazole derivative of the general formula (I) in which Q¹ is --SO₂ --R⁸ or ##STR173##

In the above step (d), the molar ratio of the compound of the general formula (Ia) to the compound of the general formula (IV) is preferably 1:1 to 1:10. The inert solvent is not specially limited if it is inert to the reaction. However, the inert solvent is preferably selected, for example, from ethers such as diethyl ether and tetrahydrofuran and halogenated hydrocarbons such as dichloromethane and chloroform. The step (d) is preferably carried out in the presence of a base such as sodium carbonate, potassium carbonate, triethylamine or pyridine generally at a temperature of From room temperature to the boiling point of the solvent. Further, the reaction may be carried out in a two-phase solvent system such as water-benzene, water-toluene, water-chloroform or waterdichloromethane. In this case, the reaction proceeds more smoothly when a phase transfer catalyst such as crown ether or benzyltriethylammonium chloride is added to the reaction system.

The pyrazole derivative of the general formula (I) in which p¹ is 1 (sulfoxide) or 2 (sulfone), i.e., a pyrazole derivative of the general formula (Ic). ##STR174## [wherein p² is 1 or 2 R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X¹, n Q¹, R⁸, Y and m¹ are as defined in the above general formula (I)]can be also produced by the following third process.

The third process comprises oxidizing the sulfur atom of the pyrazole derivative of the general formula (I) in which p¹ is 0 (sulfide), provided by the present invention, i.e., a compound of the general formula (Id), ##STR175## [wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X¹, n Q¹, R⁸, Y and m¹ are as defined in the above general formula (x)], with a proper oxidizing agent to obtain the pyrazole derivative of the general formula (Ic).

The above oxidizing agent can be selected from a variety of compounds, while it is preferably selected from hydrogen peroxide, peracetic acid and sodium metaperiodate. Hydrogen peroxide is particularly preferred.

The solvent which is to be used is not specially limited if it is inert to the reaction, while acetic acid is preferred.

The reaction temperature is preferably in the range of from room temperature to the boiling point of the solvent.

For producing the pyrazole derivative of the general formula (Ic) in which p² is 1 (sulfoxide), provided by the present invention, i.e., a pyrazole derivative of the general formula (Ie), ##STR176## [wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, X¹, n Q¹, R⁸, Y and m¹ are as defined in the above general formula (I)], the reaction is preferably carried out in the presence of the oxidizing agent in an amount of 1 equivalent around room temperature.

For producing the pyrazole derivative of the general formula (Ic) in which p² is 2 (sulfone), provided by the present invention, i.e., a pyrazole derivative of the general formula (If), ##STR177## [wherein R 1, R², R³, R⁴, R⁵, R⁶, R⁷, X¹, n Q¹, R⁸, Y and m¹ are as defined in the above general formula (I)], the reaction is preferably carried out in the presence of the oxidizing agent in an amount of at least 2 equivalents at 50° to 100° C.

The compound of the general formula (II) used as the starting material in each of the above first and second processes for the production of the pyrazole derivative of the general formula (I) is a novel intermediate compound, and can be synthesized by various methods. For example, it can be synthesized according to the following reaction scheme. ##STR178##

The steps (i), (ii), (iii) and (iv) will be explained hereinafter.

In the step (i), the thiochroman-4-one of the general formula (VII) is reduced to form an alcohol of the general formula (VIII). The reaction temperature is generally -20° C. to 50° C. The reducing agent is selected from a variety of compounds, and sodium borohydride is used for example. The thiochroman-4-one of the general formula (VII) used as a starting material can be produced by a variety of methods, such as the methods described in JP-A-58-198483, International Publication W088/06155, and Canadian Journal of Chemistry, vol. 51, page 839 (1973).

In the step (ii), the alcohol of the general formula (VIII) and the alcohol of the general formula. R¹ OH, are allowed to undergo dehydrative condensation to form an ether of the general formula (IX). The solvent is selected from aromatic hydrocarbon solvents such as benzene, toluene and xylene and halogenated hydrocarbon solvents such as 1,2-dichloroethane and carbon tetrachloride. An excess of the alcohol of R¹ OH may be used as a solvent. The catalyst is selected from acid catalysts such as sulfuric acid, aromatic sulfonic acid, aromatic sulfonic acid halide, boron trifluoride and aluminum chloride, whereby the reaction proceeds smoothly. The temperature is generally 60° C. to the boiling point of the solvent, and it is preferably the reflux temperature of the alcohol of R¹ OH.

In the step (iii), the compound of the general formula (IX) and magnesium are allowed to react to Form a Grignard reagent, and carbon dioxide is allowed to react with the Grignard reagent to form a carboxylic acid of the general formula (X). The reaction temperature is generally 0° to 50° C. The solvent to be used is preferably selected from diethyl ether and tetrahydrofuran. The compound of the general formula (X) corresponds to the compound of the general formula (II) in which p¹ is 0 (sulfide).

In the step (iv), the sulfur atom of the carboxylic acid of the general formula (X) is oxidized to form a compound of the general formula (XI), in which the compound of the general formula (XI) corresponds to compounds of the general formula (II) in which p¹ is 1 (sulfoxide) and p¹ is 2 (sulfone). The reaction temperature is generally room temperature to 100° C. The oxidizing agent is selected from a variety of compounds, and hydrogen peroxide is particularly preferred. The solvent is selected from a variety of solvents, and acetic acid is particularly preferred. For producing the compound (sulfoxide) in which p¹ is 1, the reaction is carried out in the presence of 1 equivalent of the oxidizing agent at room temperature. For producing the compound (sulfone) in which p¹ is 2, the reaction is carried out in the presence of at least 2 equivalents at 50° to 100° C.

The compound of the general formula (XII), ##STR179## [wherein X⁴ is a C₁ -C₄ alkyl group, and R¹, R², R³, R⁴ and R⁵ are as defined in the above general formula (I)], which is included in the compound of the general formula (II), can be synthesized by the above reaction scheme, while it can be also synthesized by treating the compound of the general formula (XIII) obtained by the above reaction scheme, ##STR180## [wherein X⁴ is a C₁ -C₄ alkyl group, and R¹, R², R³, R⁴ and R⁵ are as defined in the above general formula (I)], with a proper reducing agent.

The proper reducing agent is selected from a variety of compounds, while zinc is preferred. The solvent is preferably selected from water and alcohol solvents such as ethanol and a mixture of these. The reaction is carried out at a temperature in the range of room temperature to the boiling point of the solvent, preferably 80° to 100° C. Further, the reaction proceeds smoothly when a strong base such as sodium hydroxide or potassium hydroxide is added.

The compound of the general formula (II) obtained as described above is a novel compound, and can be used as a starting material for the production of the pyrazole derivative of the general formula (I).

The pyrazole compound of the general formula (III) used as a reaction agent in each of the above first and second processes can be synthesized, for example, by the method described in JP-A-61-257974.

The herbicide of the present invention contains the novel pyrazole derivative or the salt thereof, provided by the present invention, as an active ingredient, and used as follows. The pyrazole derivative or the salt thereof is mixed with a liquid carrier such as a solvent or a solid carrier such as a fine mineral powder, and the mixture is prepared into the form of a wettable powder, an emulsion, a dust or granules. For imparting these compounds with emulsifiability, dispersibility and wettability in producing the above preparations, a surfactant can be added.

When the herbicide of the present invention is used in the form of a wettable powder, a composition is prepared by mixing 10 to 55% by weight of the pyrazole derivative or the salt thereof, provided by the present invention, 40 to 88% by weight of a solid carrier and 2 to 5% by weight of a surfactant, and the resultant composition may be used. When it is used in the form of an emulsion, the emulsion can be prepared by mixing 20 to 50% by weight of the pyrazole derivative or the salt thereof provided by the present invention, 35 to 75% by weight of a solvent and 5 to 15% by weight of a surfactant.

On the other hand, when the herbicide of the present invention is used in the form of dust, generally, the dust can be prepared by mixing 1 to 15% by weight of the pyrazole derivative or the salt thereof, provided by the present invention, 80 to 97% by weight of a solid carrier and 2 to 5% by weight of a surfactant. Further, when it is used in the form of granules, the granules can be prepared by mixing 1 to 15% by weight of the pyrazole derivative or or the salt thereof, provided by the present invention, 80 to 97% by weight of a solid carrier and 2 to 5% by weight of a surfactant. This solid carrier is selected from fine mineral powders, and examples of these fine mineral powders include diatomaceous earth, oxides such as slaked lime, phosphates such as apatite, sulfates such as gypsum, and silicates such as talc, pyrophyllite, clay, kaolin, bentonite, acid clay, white carbon, powdered quartz and a silica powder.

The above solvent is selected from organic solvents, and specific examples of the organic solvents include aromatic hydrocarbons such as benzene, toluene and xylene, chlorinated hydrocarbons such as o-chlorotoluene, trichloromethane and trichloroethylene, alcohols such as cyclohexanol, amyl alcohol and ethylene glycol, ketones such as isophorone, cyclohexanone and cyclohexenyl-cyclohexanone, ethers such as butyl cellosolve, dimethyl ether and methyl ethyl ether, esters such as isopropyl acetate, benzyl acetate and methyl phthalate, amides such as dimethylformamide, and mixtures of these.

Further, the above surfactant is selected from anionic surfactants, nonionic surfactants, cationic surfactants and amphoteric surfactants (amino acid and betaine).

The herbicide of the present invention may contain other herbicidally active component as an optional active ingredient in combination with the pyrazole derivative of the formula (I) or the salt thereof. This "other" herbicidally active component includes known herbicides such as phenoxy, diphenylether, triazine, urea, carbamate, thiolcarbamate, acid anilide, pyrazole, phosphoric acid, sulfonylurea and oxadiazon herbicides. This "other" herbicide is properly selected from these herbicides.

Further, the herbicide of the present invention may be used in combination with an insecticide, a fungicide, a plant growth regulator and a fertilizer as required.

EXAMPLES

The present invention will be further explained hereinafter with reference to Examples. However, the present invention shall not be limited to these Examples.

Preparation Example 1

A) 4.4 Grams (0.017 mol) of 6-bromo-5-methylthiochroman-4-one was dissolved in 10 ml of methylene chloride and 10 ml of methanol. The solution was cooled to 0° C. with a salt water-ice bath. 0.32 Grams (0.0085 mol) of sodium borohydride was gradually added so that the temperature did not exceed 10° C. While the mixture was cooled with the ice bath, it was allowed to react for 1 hour. Then, the reaction mixture was poured into 100 ml of 5% hydrochloric acid, and extracted with methylene chloride. The methylene chloride layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. Added to the resultant oil were 20 ml of methanol and 0.3 g of concentrated sulfuric acid, arid the mixture was refluxed under heat for 2 hours. The reaction mixture was allowed to cool, poured into 200 ml of water and extracted with methylene chloride. The methylene chloride layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give 4.3 g of 6-bromo-4-methoxy-5-methylthiochroman as oil.

B) 1.75 Grams (0.021 mol) of magnesium was placed in a 500-ml three-necked flask, and 100 ml of dry tetrahydrofuran was added to suspend the magnesium therein. Then, 4.3 g (0.016 mol) of 6-bromo-4-methoxy-5-methylthiochroman obtained in A) and 3.5 g (0.032 mol) of ethyl bromide were added, and the mixture was refluxed under heat for 3 hours. The reaction mixture was allowed to cool, and then cooled with an ice bath. When the internal temperature was decreased to 10° C., carbon dioxide gas was bubbled. After the bubbling was carried out for 30 minutes, the reaction mixture was again cooled with the ice bath, and when the temperature was 10° C., 200 ml of 5% hydrochloric acid was added to remove an excess of magnesium. The reaction mixture was extracted with ethyl acetate. The ethyl acetate layer was extracted with 100 ml of a 5% potassium carbonate aqueous solution three times. To the resultant potassium carbonate solution was added 10% hydrochloric acid to adjust the pH to 1. A precipitated solid was recovered by filtration, and dried to give 2.9 g (0.012 mol) of 4-methoxy-5-methylthiochroman-6-carboxylic acid (Compound 1). The yield from the 6-bromo-5-methylthiochroman-4-one was 71%.

Preparation Examples 2-10

Compounds 2-10 shown in Table 2, right column, were obtained in the same manner as in Example 1 except that the 6-bromo-5-methylthiochroman-4-one as the starting material was replaced with compounds shown in Table 2, left column.

Preparation Examples 11-14

Compounds 11-14 shown in Table 2, right column, were obtained in the same manner as in Example 1 except that the 6-bromo-5-methylthiochroman-4-one as the starting material was replaced with compounds shown in Table 2, left column and that the methanol in Preparation Example 1 was replaced with ethanol.

Preparation Example 15

8-Chloro-4-n-propoxy-5-methylthiochroman-6-carboxylic acid (Compound 15) shown in Table 2 was obtained in the same manner as in Example 1 except that the 6-bromo-5-methylthiochroman-4-one in Example 1 was replaced with 6-bromo-8-chloro-5-methylthiochroman-4-one and that the methanol was replaced with n-propanol.

Preparation Example 16

8-Chloro-4-i-propoxy-5-methylthiochroman-6-carboxylic acid (Compound 16) shown in Table 2 was obtained in the same manner as in Example 1 except that the 6-bromo-5-methylthiochroman-4-one in Example 1 was replaced with 6-bromo-8-chloro-5-methylthiochroman-4-one and that the methanol was replaced with i-propanol.

Preparation Example 17

5,8-Dimethyl-4-n-butoxythiochroman-6-carboxylic acid (Compound 17) shown in Table 2 was obtained in the same manner as in Example 1 except that the 6-bromo-5-methylthiochroman-4-one in Example 1 was replaced with 6-bromo-5.8-dimethylthiochroman-4-one and that the methanol was replaced with n-butanol.

Preparation Example 18

A 50-ml egg-plant type flask was charged with 4.8 g (0.02 mol) of 4-methoxy-5-methylthiochroman-6-carboxylic acid, 20 ml of acetic acid and 6.8 g (0.06 mol) of a 30% hydrogen peroxide aqueous solution and the mixture was heated at 100° C. for 1 hour. After allowed to cool, the reaction mixture was poured into 100 ml of water. The precipiated oil was extracted with ethyl acetate, and the extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 4.6 g of 4-methoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide (Compound 18) shown in Table 2.

Preparation Examples 19-30

Compounds 19 to 30 shown in Table 2, right column, were obtained in the same manner as in Preparation Example 18 except that the 4-methoxy-5-methylthiochroman-6-carboxylic acid used as the starting material in Preparation Example 18 was replaced with starting materials shown in Table 2, left column.

Preparation Example 31

A 50-ml egg-plant type Flask was charged with 2.9 g (0.011 mol) of 4-ethoxy-5,8-dimethylthiochroman-6-carboxylic acid, 10 ml of acetic acid and 1.3 g (0.011 mol) of a 30% hydrogen peroxide aqueous solution, and the mixture was allowed to react at room temperature for 12 hours. Then, the reaction mixture was poured into 100 ml of water. The precipitated oil was extracted with ethyl acetate, and the extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 2.5 g of 4-ethoxy-5,8-dimethylthiochroman-6-carboxylic acid-1-oxide (Compound 31) shown in Table 2.

Preparation Example 32

A 50-ml egg-plant type flask was charged with 1.36 g (0.0041 mol) of 8-chloro-4-n-propoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide, 1.35 g (0.02 mol) of potassium hydroxide, 0.81 g (0.012 mol) of a zinc powder, 10 ml of water and 6 ml of ethanol, and the mixture was refluxed under heat for 10 hours. After allowed to cool, insolubles were removed by filtration, and the ethanol was distilled off under reduced pressure. Then, while the remainder was cooled with ice, 50 ml of 5% hydrochloric acid was added to adjust the pH to 1. The reaction mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with 2% hydrochloric acid, washed with a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 1.0 g of 4-n-propoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide (Compound 32) shown in Table 2.

Preparation Example 33

1.1 Grams of 4-i-propoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide (Compound 33) shown in Table 2 was obtained in the same manner as in Example 32 except that the 8-chloro-4-n-propoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide in Preparation Example 32 was replaced with 8-chloro-4-i-propoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide.

Table 2 shows the structures and yields of Compounds 1 to 33 obtained in the above Examples 1 to and Table 33 shows the physical properties thereof.

                                      TABLE 2                                      __________________________________________________________________________     Prep.                                                                               Starting          Prepared                                                                             Structural        Yield                           Ex. No.                                                                             material          Compd No.                                                                            formula           (%)                             __________________________________________________________________________      1                                                                                   ##STR181##        1                                                                                    ##STR182##       71                               2                                                                                   ##STR183##        2                                                                                    ##STR184##       30                               3                                                                                   ##STR185##        3                                                                                    ##STR186##       22                               4                                                                                   ##STR187##        4                                                                                    ##STR188##       52                               5                                                                                   ##STR189##        5                                                                                    ##STR190##       74                               6                                                                                   ##STR191##        6                                                                                    ##STR192##       19                               7                                                                                   ##STR193##        7                                                                                    ##STR194##       70                               8                                                                                   ##STR195##        8                                                                                    ##STR196##       38                               9                                                                                   ##STR197##        9                                                                                    ##STR198##       77                              10                                                                                   ##STR199##       10                                                                                    ##STR200##       32                              11                                                                                   ##STR201##       11                                                                                    ##STR202##       60                              12                                                                                   ##STR203##       12                                                                                    ##STR204##       83                              13                                                                                   ##STR205##       13                                                                                    ##STR206##       87                              14                                                                                   ##STR207##       14                                                                                    ##STR208##       54                              15                                                                                   ##STR209##       15                                                                                    ##STR210##       71                              16                                                                                   ##STR211##       16                                                                                    ##STR212##       51                              17                                                                                   ##STR213##       17                                                                                    ##STR214##       71                              18                                                                                   ##STR215##       18                                                                                    ##STR216##       85                              19                                                                                   ##STR217##       19                                                                                    ##STR218##       74                              20                                                                                   ##STR219##       20                                                                                    ##STR220##       68                              21                                                                                   ##STR221##       21                                                                                    ##STR222##       89                              22                                                                                   ##STR223##       22                                                                                    ##STR224##       91                              23                                                                                   ##STR225##       23                                                                                    ##STR226##       73                              24                                                                                   ##STR227##       24                                                                                    ##STR228##       90                              25                                                                                   ##STR229##       25                                                                                    ##STR230##       95                              26                                                                                   ##STR231##       26                                                                                    ##STR232##       87                              27                                                                                   ##STR233##       27                                                                                    ##STR234##       91                              28                                                                                   ##STR235##       28                                                                                    ##STR236##       100                             29                                                                                   ##STR237##       29                                                                                    ##STR238##       93                              30                                                                                   ##STR239##       30                                                                                    ##STR240##       97                              31                                                                                   ##STR241##       31                                                                                    ##STR242##       81                              32                                                                                   ##STR243##       32                                                                                    ##STR244##       83                              33                                                                                   ##STR245##       33                                                                                    ##STR246##       93                              __________________________________________________________________________

                  TABLE 3                                                          ______________________________________                                         Compd Infrared absorption                                                                          Proton nuclear magnetic                                    No.   spectrum *1 (cm.sup.-1)                                                                      resonance spectrum (ppm)                                   ______________________________________                                          1    1700(C═O) 1.5˜1.95(H, m)2.45˜2.95(2H, m)                       2880, 2960,   2.65(3H, s)3.10˜3.36(H, m)                                 3000(C--H)    3.46(3H, s)4.53˜4.63(H, m)                                 2550˜3450(O--H)                                                                        7.05(H, d)7.78(H, d)                                                           *2                                                          2    1695(C═O) 1.52˜1.93(H, m)2.50˜2.90(2H, m)                      2830, 3000(C--H)                                                                             2.60(3H, s)3.03˜3.35(H, m)                                 2550˜3450(O--H)                                                                        3.48(3H, s)4.50˜4.60(H, m)                                               7.56(H, d)                                                                     *2                                                          3    1695(C═O) 1.50˜1.90(H, m)2.55˜3.00(2H, m)                      2950, 3000(C--H)                                                                             3.14˜3.44(H, m)3.50(3H, s)                                 2550˜3450(O--H)                                                                        4.85˜4.98(H, m)7.93(H, s)                                                *2                                                          4    1695(C═O) 1.43˜1.60(3H, m)2.10˜2.85(2H, m)                     2820, 2880, 2930,                                                                            2.70(3H, s)3.20˜3.30(H, m)                                 2980(C--H)    3.46(3H, s)4.54˜4.75(H, m)                                 2550˜3450(O--H)                                                                        7.56(H, d)                                                                     *2                                                          5    1695(C═O) 1.46˜1.87(H, m)2.60(3H, s)                                 2830, 2940,   2.70˜3.05(2H, m)3.15˜3.37(H, m)                      3000(C--H)    3.45(3H, s)4.60˜4.70(H, m)                                 2550˜3450(O--H)                                                                        7.80(H, s)                                                                     *3                                                          6    1710(C═O) 0.88(3H, d)2.55˜2.85(2H, m)                                2550, 2950,   3.10˜3.35(H, m)                                            2990(C-- H)   3.47(3H, s)4.60˜4.70(H, m)                                 2550˜3450(O--H)                                                                        7.90(H, s)9.75(H, s, broad)                                                    *2                                                          7    1700(C═O) 1.50˜1.93(H, m)2.25(3H, s)                                 2960, 3000(C--H)                                                                             2.50˜2.90(2H, m)2.63(3H, s)                                2500˜3500(O--H)                                                                        3.10˜3.30(H, m)3.46(3H, s)                                               4.56˜4.66(H, m)7.72(H, s)                                                *2                                                          8    1700(C═O) 1.43˜1.90(H, m)2.46˜3.00(2H, m)                      2850, 2950,   3.13˜3.37(H, m)3.46(3H, s)                                 3000(C--H)    4.65˜4.82(H, m)7.46˜7.72(H, m)                       2550˜3450(O--H)                                                                        9.3(H, s, broad)                                                               *2                                                          9    1710(C═O) 0.92(3H, d)2.28(3H, s)                                           2850, 3000(C--H)                                                                             2.54˜2.76(2H, m)2.62(3H, s)                                2550˜3450(O--H)                                                                        3.33˜3.60(H, m)3.45(3H, s)                                               4.25˜4.35(H, m)7.72(H, s)                                                *2                                                         10    1730(C═O) 1.54˜1.95(H, m)2.30(3H, s)                                 2950(C--H)    2.39(3H, s)2.55˜2.80(2H, m)                                2650˜3450(O--H)                                                                        3.08˜3.30(H, m)3.44(3H, s)                                               4.40˜4.50(H, m)6.87(H, s)                                                7.10(H, s, broad) *2                                       11    1695(C═O) 1.27(3H, t)1.43(3H, d)                                           2870, 2940,   2.50˜2.85(2H, m)2.64(3H, s)                                2980(C--H)    3.35˜3.72(H, m)3.78(2H, q)                                 2550˜3450(O--H)                                                                        4.62˜4.72(H, m)7.60(H, d)                                                *2                                                         12    1695(C═O) 1.20(3H, t)2.30˜3.10(2H, m)                                2940, 3000(C--H)                                                                             2.61((3H, s)3.20˜3.70(2H, m)                               2550˜3450(O═H)                                                                     3.66˜ 3.90(2H, m)4.77˜4.84(H, m)                                   7.77(H, d)7.98(H, d)                                                           9.5(H, s, broad) *3                                        13    1695(C═O) 1.25(3H, t)1.50˜1.95(H, m)                                 2880, 2940,   2.25(3H, s)2.62(3H, s)                                           2980(C--H)    2.50˜2.90(2H, m)                                           2550˜3450(O--H)                                                                        3.10˜3.37(H, m)3.75(2H, q)                                               4.63˜4.75(H, m)7.70(H, s) *2                         14    1670(C═O) 1.22(3H, t)1.50˜1.90(H, m)                                 2930, 2970(C--H)                                                                             2.40˜3.0(2H, m)3.20˜3.50(H, m)                       2500˜3200(O--H)                                                                        3.50˜3.90(2H, m)4.80˜4.95(H, m)                                    7.60 (H, t) 9.8 (H, s, broad)                                                  *2                                                         15    1695(C═O) 0.93(3H, t)1.40˜1.95(3H, m)                                2880, 2950,   2.65(3H, s)2.30˜3.0(2H, m)                                 2990(C--H)    3.20˜3.85(3H, m)4.80˜4.95(H, m)                      2550˜3450(O--H)                                                                        7.80(H, s) *2                                              16    1700(C═O) 1.23(6H, dd)1.46˜1.86(H, m)                                2900, 2950,   2.65(3H, s)2.70˜3.00(2H, m)                                2990(C--H)    3.13˜3.45(H, m)3.84˜4.20(H, m)                       2550˜3450(O--H)                                                                        4.95˜5.05(H, m)7.80(H, s) *3                         17    1680(C═O) 0.91(3H, t)1.20˜1.92(5H, m)                                2860, 2930,   2.25(3H, s)2.62(3H, s)                                           2960(C--H)    2.50˜2.90(2H, m)3.10˜3.35(H, m)                      2550˜3450(O--H)                                                                        3.65˜3.85(2H, m)4.60˜4.70(H, m)                                    7.70(H, s) *2                                              18    1730(C═O) 2.40˜2.75(2H, m)                                           2890, 3000(C--H)                                                                             2.60(3H, s)2.80˜3.70(2H, m)                                2550˜3450(O--H)                                                                        3.50(3H, s)4.70˜4.80(H, m)                                 1130, 1280(SO.sub.2)                                                                         7.76(H, d)7.97(H, d) *3                                    19    --            2.30˜2.90(2H, m)2.50(3H, s)                                              3.15˜3.90(2H, m)3.51(3H, s)                                              4.45˜4.55(H, m)7.70(H, d)                                                *2                                                         20    --            2.40˜2.95(2H, m)3.20˜3.85(2H, m)                                   3.50(3H, s)4.55˜4.60(H, m)                                               7.60(H, s)                                                                     *2                                                         21    --            1.58(3H, t)2.50˜2.70(2H, m)                                              2.54(3H, s)3.42(H, m)3.49(3H, s)                                               4.46˜4.60(H, m)7.65(H, d)                                                9.8 (H, s, broad)                                                              *2                                                         22    1700(C═O) 2.23˜2.50(H, m)2.58(3H, s)                                 2840, 2960,   2.77˜3.07(H, m)3.20˜3.90(2H, m)                      3000(C--H)    3.51(3H, s)4.70˜4.77(H, m)                                 2550˜3500(O--H)                                                                        7.89(H, s)                                                       1140, 1300(SO.sub.2)                                                                         *3                                                         23    1730(C═O) 1.20(3H, t)2.30˜3.10(2H, m)                                2880, 2940(C--H),                                                                            2.61(3H, s)3.20˜3.70(2H, m)                                2550˜3500(O--H)                                                                        3.66˜3.90(2H, m)                                           1140, 1300(SO.sub.2)                                                                         4.77˜4.84(H, m)7.77(H, d)                                                7.98(H, d)9.5(H, s, broad) *3                              24    1730(C═O) 2.45˜2.95(2H, m)2.53(3H, s)                                2960, 3000(C--H)                                                                             2.73(3H, s)3.20˜3.35(H, m)                                 2550˜3450(O--H)                                                                        3.46(3H, s)3.63˜3.86(H, m)                                 1110, 1280(SO.sub.2)                                                                         4.50˜4.60(H, m)7.70(H, s)                                                *2                                                         25    1730(C═O) 1.26(3H, t)2.30˜2.90(2H, m)                                2900, 2950,   2.54(3H, s)2.74(3H, s)                                           3000(C--H)    3.10˜4.0(2H, m)3.54˜3.88(2H, m)                      2500˜3500(O--H)                                                                        4.62˜4.68(H, m)7.69(H, s)                                  1125, 1285(SO.sub.2)                                                                         *2                                                         26    1730(C═O) 0.92(3H, t)1.20˜1.80(4H, m)                                2900, 2960,   2.30˜2.90(2H, m)2.58(3H, s)                                2980(C--H)    2.77(3H, s)3.10˜4.05(4H, m)                                2600˜3450(O--H)                                                                        4.60˜4.70(H, m)6.66 (H, s, broad)                          1130, 1290(SO.sub.2)                                                                         7.77(H, s) *2                                              27    1730(C═O) 1.19˜1.38(3H, m)2.56(3H, s)                                2940, 2990(C--H)                                                                             2.74(3H, s)2.85˜3.35(2H, m)                                2750˜3450(O--H)                                                                        3.42(3H, s)3.85˜4.05(H, m)                                 1110, 1285(SO.sub.2)                                                                         4.43˜4.58(H, m)7.69(H, s)                            28    1730(C═O) 2.39(6H, s)2.30˜2.80(2H, m)                                2850, 2960(C--H)                                                                             3.10˜3.90(2H, m)3.47(3H, s)                                2600˜3500(O--H)                                                                        4.40˜4.50(H, m)                                            1140, 1300(SO.sub.2)                                                                         7.64(H, m)                                                                     *2                                                         29    --            0.93(3H, t)1.40˜1.85(2H, m)                                              2.40˜3.05(2H, m)2.55(3H, s)                                              3.30˜3.90(4H, m)4.75˜4.85(H, m)                                    7.88(H, s)                                                                     *3                                                         30    --            1.24(6H, dd)2.30˜2.55(H,                                                 m)2.58(3H, s)                                                                  2.85˜3.15(H, m)3.20˜3.45(H, m)                                     3.53˜3.77(H, m)3.87˜4.20(H, m)                                     5.0˜5.10(H, m)7.90(H, s)                                                 *3                                                         31    1725(C═O) 1.24(3H, t)2.30˜2.95(2H, m)                                2940, 2980(C--H)                                                                             2.53(3H, s)2.70(3H, s)                                           2500˜3450(O--H)                                                                        3.05˜3.50(2H, m)3.66(2H, q)                                980(SO)       4.58˜4.73(H, m)7.67(H, s)                                                *2                                                         32    1730(C═O) 0.94(3H, t)1.40˜1.85(2H, m)                                2950, 3000(C--H)                                                                             2.45˜3.0(2H, m)2.62(3H, s)                                 2550˜3450(O--H)                                                                        3.20˜3.85(4H, m)4.80˜4.90(H, m)                      1140, 1300(SO.sub.2)                                                                         7.75(H, d)7.95(H, d)                                                           *3                                                         33    1730(C═O) 1.25(6H, dd)2.25˜2.50(H, m)                                2940, 2980(C--H)                                                                             2.65(3H, s)2.80˜3.10(H, m)                                 2550˜3450(O--H)                                                                        3.20˜3.50(H, m)3.55˜3.75(H, m)                       1120, 1305(SO.sub.2)                                                                         3.85˜4.20(H, m)5.0˜5.10(H, m)                                      7.75(H, d)7.95(H, d) *3                                    ______________________________________                                          *1 KBr tablet method                                                           *2 Solvent/deutero chloroform Internal standard/tetramethylsilane              *3 Solvent/deutero acetone Internal standard/tetramethylsilane           

Preparation Example 34

A 100-ml flask was charged with 1.0 g (0.0037 mol) of 4-methoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide shown in Table 5, left column, and 5.0 ml of thionyl chloride, and the mixture was allowed to react at 60° C. for 30 minutes. After the reaction was completed, an excess of thionyl chloride was distilled off under reduced pressure. The remaining oil was dissolved in 5,0 ml of chloroform, and was added to a mixture of 0.41 g (0.0037 mol) of 1-ethyl-5-hydroxypyrazole, 0.37 g (0.0037 mol) of triethylamine and 20 ml of chloroform in another 200-ml flask, and the resultant mixture was allowed to react. After the mixture was allowed to react at room temperature for 2 hours, the reaction mixture was washed with 5% hydrochloric acid and dried over anhydrous sodium sulfate, and the chloroform was distilled off under reduced pressure. Added to the remaining oil were 0.77 g (0.0056 mol) of anhydrous potassium carbonate and 1.0 ml of 1,4-dioxane, and the mixture was allowed to react at 130° C. for 2 hours. After allowed to cool, the reaction mixture was dissolved by adding 20 ml of water, and washed with ether. The aqueous layer was separated, and 5% hydrochloric acid was added to adjust the pH to 1. The precipitated oil was extracted with ethyl acetate, and the extract was dried over anhydrous sodium sulfate. Then, the ethyl acetate was distilled off under reduced pressure to give 4-methoxy-5-methyl-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 34) shown in Table 5, right column.

Preparation Examples 35-37

Compounds 35 to 37 of which the structural formulae are shown in Table 5, right column, were obtained. in the same manner as in Preparation Example 54 except that the 4-methoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide in Preparation Example 54 was replaced with starting materials shown in Table 5, left column.

Preparation Example 38

0.60 Gram of 5,8-dichloro-4-methoxy-6-(1,3-dimethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 38) shown in Table 5 was obtained in the same manner as in Preparation Example 34 except that the 4-methoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide in Preparation Example 34 was replaced with 5,8-dichloro-4-methoxythiochroman-6-carboxylic acid-1,1-dioxide and that the 1-ethyl-5-hydroxypyrazole in Preparation Example 34 was replaced with 1,3-dimethyl-5-hydroxypyrazole. The Yield thereof was 47%.

Preparation Example 39

4-Ethoxy-5-methyl-6- (1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 39) shown in Table 5, right column, was obtained in the same manner as in Preparation Example 34 except that the 4-methoxy-5-methylthiochroman-6-carboxylic acid-1,1-dioxide in Preparation Example 34 was replaced with a starting material shown in Table 5, left column.

Preparation Example 40

In a 50-ml flask, 0.70 g (0.0023 mol) of 8-fluoro-4-methoxy-2,5-dimethylthiochroman-6-carboxylic acid-1,1-dioxide, 0.28 g (0.0025 mol) of 1-ethyl-5-hydroxypyrazole and 0.52 g (0. 0025 mol) of DCC (N,N'-dicyclohexylcarbodiimide) were added to 5 ml of tert-amyl alcohol at the same time, and the mixture was stirred at room temperature for 30 minutes. Then, 0.17 g (0.00125 mol) of anhydrous potassium carbonate was added. The reaction mixture was allowed to react at 80° C. for 8 hours, and then the reaction solvent was distilled off under reduced pressure. The remainder was dispersed in a 2% potassium carbonate aqueous solution and ethyl acetate to separate it into two phases. Further, the aqueous phase was acidified with 5% hydrochloric acid, and the precipitated oil was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to give 0.70 g of 8-fluoro-4-methoxy-2,5-dimethyl-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 40) shown in Table 5. The yield thereof was 78%.

Preparation Examples 41, 53 and 56

Compounds 41, 53 and 56 of which the structural formulae are shown in Table 5, right column, were obtained in the same manner as in Preparation Example 40 except that the 6-fluoro-4-methoxy-2,5-dimethylthiochroman-6-carboxylic acid-1,1-dioxide in Preparation Example 40 was replaced with starting materials shown in Table 5, left column and that the 1-ethyl-5-hydroxypyrazole was replaced with 1,3-dimethyl-5-hydroxypyrazole.

Preparation Examples 42-52 and 55

Compounds 42 to 52 and 55 of which the structural formulae are shown in Table 5, right column were obtained in the same manner as in Preparation Example 40 except that the 6-fluoro-4-methoxy-2,5-dimethylthiochroman-6-carboxylic acid-1,1-dioxide in Preparation Example 40 was replaced with starting materials shown in Table 5, left column.

Preparation Example 54

4-Methoxy-5-methyl-6-(1-methyl-5-hydroxypyrazole-4-yl)carbonylthiochroman-1,1-dioxide (Compound 54 ) shown in Table 5 was obtained in the same manner as in Preparation Example 40 except that the 6-fluoro-4-methoxy-2,5-dimethylthiochroman-6-carboxylic acid-1,1-dioxide in Preparation Example 40 was replaced with a starting material shown in Table 5 and that the 1-ethyl-5-hydroxypyrazole was replaced with 1-methyl-5-hydroxypyrazole.

Preparation Example 57

A 50-ml egg-plant type flask was charged with 1.7 g (0. 0057 mol) of 4-methoxy-3,5,8-trimethylthiochroman-6-carboxylic acid-1,1-dioxide (Compound 27) and 0.64 g (0.0057 mol) of 1-ethyl-5-hydroxypyrazole, and then the mixture was suspended in 20 ml of methylene chloride. Then, 1.24 g (0.0060 mol) of DCC was added, and the mixture was allowed to react at room temperature for 8 hours. After the reaction was completed, insolubles were removed by filtration, and the methylene chloride was distilled off under reduced pressure to give an oil. This oil was purified by silica gel column chromatography to give 0.8 g of Compound A and 0.3 g of Compound B as a solid each. These Compounds were analyzed to show that Compound B was 3,4-trans-4-methoxy-3,5,8-trimethyl-6-(1-ethylpyrazol-4-yl)oxycarbonylthiochroman-1,1-dioxide and that Compound A was 3,4-cis-4-methoxy-3,5,8-trimethyl-6- (1-ethylpyrazol-4-yl)oxycarbonyl-thiochroman-1,1-dioxide. Table 4 shows the structures arid physical properties of Compounds A and B.

                                      TABLE 4                                      __________________________________________________________________________                                Proton nuclear magnetic                                                        resonance spectrum*                                 Compd                                                                              Structural formula     (ppm)                                               __________________________________________________________________________          ##STR247##            1.27(3H, d)1.44(3H, t) 2.63(3H, s)2.81(3H, s)                                  2.90˜3.20(H, m)3.25˜3.35(H, m)                                     3.45(3H, s)3.93(H, d) 4.09(2H, q)4.47(2H,                                      d)6.24(H, d) 7.49(H, d)7.84(H, s)                   B                                                                                   ##STR248##            1.37(3H, d)1.44(3H, t) 2.67(3H, s)2.81(3H, s)                                  3.05˜3.15(H, m)3.20˜3.30(H, m)                                     3.48(3H, s)3.86(H, d) 4.09(2H, q)4.61(H,                                       s)6.25(H, d)  7.49(H, d)7.84(H,                     __________________________________________________________________________                                s)                                                   *Solvent CDCl.sub.3 Internal standard tetramethylsilane                  

A 50-ml egg-plant type Flask was charged with 0.8 g (0.0020 mol) of Compound A and 0.41 g (0.003 mol) of potassium carbonate, and 2.0 ml of 1,4-dioxane was added. Then, the mixture was heated at 130° C. for 2 hours. After the reaction mixture was allowed to cool, the reaction mixture, 50 ml of ethyl acetate and 50 ml of a 5% potassium carbonate aqueous solution were added, and the aqueous layer was separated. Added to the aqueous layer was 5% hydrochloric acid to adjust the pH to 1, and the formed oil was extracted with methylene chloride. The extract was dried over sodium sulfate, and then the methylene chloride was distilled off under reduced pressure to give 0.8 g (0.0020 mol) of 3,4-trans-4-methoxy-3,5,8-trimethyl-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 57) shown in Table 5. The yield thereof from Compound 27 was 35%.

Preparation Example 58

A 50-ml egg-plant type flask was charged with 0.3 g (0.00076 mol) of Compound B and 0.16 g (0.0012 mol) of potassium carbonate, and 1,0 ml of 1,4-dioxane was added. Then, the mixture was heated at 130° C. for 2 hours. Thereafter, the reaction mixture was treated in the same manner as in Preparation Example 57 to give 0.24 g (0.00061 mol) of 3,4-cis-4-methoxy-3,5,8-trimethyl-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 58) shown in Table 5. The yield thereof from Compound B was 80%.

Preparation Example 59

A 50-ml egg-plant type flask was charged with 4.8 g (0.013 mol) of 8-fluoro-4-ethoxy-2,5-dimethyl-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman (Compound 43), 20 ml of acetic acid and 4.5 g (0.04 mol) of a 30% hydrogen peroxide aqueous solution and the mixture was heated at 100° C. for 1 hour. After allowed to cool, the reaction mixture was poured into 100 ml of water. The precipitated oil was extracted with ethyl acetate and the extract was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to give 4.6 g of 8-fluoro-4-ethoxy-2,5-dimethyl-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonyl-thiochroman-1,1-dioxide (Compound 59) shown in Table 5.

Preparation Examples 60-62

Compounds 60 to 62 of which the structural formulae are shown in Table 5, right column, were obtained in the same manner as in Preparation Example 59 except that Compound 43 used as the starting material in Preparation Example 59 was replaced with starting materials shown in Table 5, left column.

Preparation Example 63

A 50-ml egg-plant type flask was charged with 0.50 g (0.0013 mol) of Compound 46 obtained in Preparation Example 46, 0.15 g (0.0013 mol) of a 30% hydrogen peroxide aqueous solution and 1.0 ml of acetic acid, and the mixture was allowed to react at room temperature for 3 days. After the reaction was completed, 10 ml of a 1% sodium hydrogensulfite was added, and the mixture was extracted with methylene chloride. The solvent was distilled off under reduced pressure to give 0.47 g (0.0012 mol) of 5,8-dimethyl-4-methoxy-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1-oxide (Compound 63) shown in Table 5. The yield thereof was 92%.

Preparation Example 64

0.60 Gram (0.0016 mol) of 8-fluoro-4-methoxy-5-methyl-6-(1-ethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide obtained in Preparation Example 35, 0.23 g (0. 0020 mol) of methanesulfonyl chloride and 0.21 g (0. 0021 mol) of triethylamine were mixed in 10 ml of methylene chloride, and then the mixture was stirred at room temperature for 2 days. The reaction mixture was diluted with methylene chloride, washed with water and further washed with a saturated sodium hydrogencarbonate aqueous solution. The washed reaction mixture was dried over anhydrous sodium sulfate, and the methylene chloride was distilled off under reduced pressure to give 0.20 g of 8-fluoro-4-methoxy-5-methyl-6-(1-ethyl-5-methanesulfonyloxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 64) shown in Table 5. The yield thereof was 28%.

Preparation Example 65

8-Fluoro-4-methoxy-5-methyl-6-(1-ethyl-5-p-toluenesulfonyloxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 65) shown in Table 5 was obtained in the same manner as in Preparation Example 64 except that the methanesulfonyl chloride in Preparation Example 64 was replaced with p-toluenesulfonyl chloride.

Preparation Example 66

0.70 Gram (0.0019 mol) of Compound 34 obtained in Preparation Example 34 was placed in a 100-ml egg-plant type flask, and 20 ml of methylene chloride was added to dissolve Compound 34. Then, a solution of 0.30 g (0.002 mol) of potassium carbonate in 30 ml of water was added. Further, 0.55 g (0.0029 mol) of p-toluenesulfonyl chloride and 0.05 g (0.00022 mol) of benzyltriethylammonium chloride were added. The mixture was allowed to react at room temperature for 3 hours, and further refluxed under heat for 3 hours. After the reaction mixture was allowed to cool, the methylene chloride layer was separated and dried over sodium sulfate. The solvent was removed under reduced pressure to obtain an oil, and the oil was purified by silica gel column chromatography to give 0.70 g (0.0014 mol) of 4-methoxy-5-methyl-6-(1-ethyl-5-p-toluenesulfonyloxypyrazol-4-yl)-carbonylthiochroman-1,1-dioxide (Compound 66) shown in Table 5. The yield thereof was 74%.

Preparation Example 67

4-Methoxy-5-methyl-6- (1-ethyl-5-n-propanesulfonyloxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 67) shown in Table 5 was obtained in the same manner as in Preparation Example 66 except that the p-toluenesulfonyl chloride in Preparation Example 66 was replaced with n-propanesulfonyl chloride.

Preparation Example 68

4-Methoxy-5,8-dimethyl-6-(1-ethyl-5-p-toluenesulfonyloxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 68) shown in Table 5 was obtained in the same manner as in Preparation Example 66 except that Compound 34 used as the starting material in Preparation Example 66 was replaced with Compound 47.

Preparation Example 69

4-Methoxy-5,8-dimethyl-6-(1-ethyl-5-n-propanesulfonyloxypyrazol-4-yl)carbonylthiochroman (Compound 69) shown in Table 5 was obtained in the same manner as in Preparation Example 66 except that Compound 34 used as the starting material in Preparation Example 66 was replaced with Compound 46 and that the p-toluenesulfonyl chloride was replaced with n-propanesulfonyl chloride.

Preparation Example 70

4-Methoxy-5,8-dimethyl-6-(1-ethyl-5-p-chlorobenzenesulfonyloxypyrazol-4-yl)carbonylthiochroman (Compound 70) shown in Table 5 was obtained in the same manner as in Preparation Example 69 except that the n-propanesulfonyl chloride in Preparation Example 69 was replaced with p-chlorobenzenesulfonyl chloride.

Preparation Example 71

4-Methoxy-5,8-dimethyl-6-(1-ethyl-5-i-butanesulfonyloxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 71) shown in Table 5 was obtained in the same manner as in Preparation Example 68 except that the p-toluenesulfonyl chloride in Preparation Example 68 was replaced with i-butanesulfonyl chloride.

Preparation Example 72

4-Methoxy-5,8-dimethyl-6-(1-ethyl-5-benzenesulfonyloxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 72) shown in Table 5 was obtained in the same manner as in Preparation Example 68 except that the p-toluenesulfonyl chloride in Preparation Example 68 was replaced with benzenesulfonyl chloride.

Preparation Example 73

4-Methoxy-5,8-dimethyl-6-(1-ethyl-5-(2,5-dichlorobenzenesulfonyl)oxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 73) shown in Table 5 was obtained in the same manner as in Preparation Example 68 except that the p-toluenesulfonyl chloride in Preparation Example 68 was replaced with 2,5-dichlorobenzenesulfonyl chloride.

Preparation Example 74

A 50-ml egg-plant type flask was charged with 1.1 g (0.0024 mol) of Compound 69 obtained in Preparation Example 69, 3.0 ml of acetic acid and 0.70 g (0.0062 mol) of a 30% hydrogen peroxide aqueous solution, and the mixture was heated at 80° C. for 3 hours. After the reaction mixture was allowed to cool, 30 ml of a 1% sodium hydrogensulfite aqueous solution was added, and the mixture was extracted with methylene chloride. The methylene chloride layer was washed with a saturated sodium bicarbonate aqueous solution and dried over sodium sulfate. The methylene chloride was distilled under reduced pressure to give 0.85 g (0.0018 mol) of 4-methoxy-5,8-dimethyl-6-(1-ethyl-5-n-propanesulfonyloxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 74) shown in Table 5. The yield thereof was 75%.

Preparation Example 75

A 50-ml egg-plant type flask was charged with 1.2 g (0.0025 mol) of Compound 70 obtained in Preparation Example 70, 3.0 ml of acetic acid and 0.71 g (0.0063 mol) of a 30% hydrogen peroxide aqueous solution, and the mixture was heated at 80° C. for 3 hours. After the reaction mixture was allowed to cool, 30 ml of a 1% sodium hydrogensulfite aqueous solution was added, and the mixture was extracted with methylene chloride. The methylene chloride layer was washed with a saturated sodium bicarbonate aqueous solution and dried over sodium sulfate. The methylene chloride was distilled under reduced pressure to give 0.99 g (0.0019 mol) of 4-methoxy-5,8-dimethyl-6-(1-ethyl-5-p-chlorobenzenesulfonyloxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 75) shown in Table 5. The yield thereof was 76%.

Preparation Example 76

A 50-ml egg-plant type flask was charged with 0.5 g (0.0010 mol) of Compound 70 obtained in Preparation Example 70, 1.0 ml of acetic acid arid 0.15 g (0.0013 mol) of a 30% hydrogen peroxide aqueous solution, and the mixture was allowed to react at room temperature for 24 hours. After the reaction was completed, 30 ml of a 1% sodium hydrogensulfite aqueous solution was added, and the mixture was extracted with methylene chloride. The methylene chloride layer was washed with a saturated sodium bicarbonate aqueous solution and dried over sodium sulfate. The methylene chloride was distilled under reduced pressure to give 0.44 g (0.00087 mol) of 4-methoxy-5,8-dimethyl-6-(1-ethyl-5-p-chlorobenzenesulfonyloxypyrazol-4-yl)carbonylthiochroman-1-oxide (Compound 76) shown in Table 5. The yield thereof was 87%.

Preparation Example 77

A 50-ml egg-plant type flask was charged with 0.75 g (0.0022 mol) of Compound 56 obtained in Preparation Example 56, 2.0 ml of acetic acid and 0.62 g (0.0055 mol) of a 30% hydrogen peroxide aqueous solution, and the mixture was allowed to react at 80° C. for 2 hours. After the reaction was completed, 20 ml of a 1% sodium hydrogensulfite aqueous solution was added, and the mixture was extracted with methylene chloride. The methylene chloride layer was dried over sodium sulfate. The methylene chloride was distilled under reduced pressure to give 0.78 g (0.0021 mol) of 4-methoxy-5,8-dimethyl-6-(1,3-dimethyl-5-hydroxypyrazol-4-yl)carbonylthiochroman-1,1-dioxide (Compound 77) shown in Table 5. The yield thereof was 95%.

Preparation Example 78

0.63 Gram (0.0017 mol) of Compound 77 obtained in Preparation Example 7V was placed in a 100-ml egg-plant type flask, and 20 ml of methylene chloride was added to dissolve Compound 77. Then, a solution of 0.28 g (0.002 mol) of potassium carbonate in 30 ml of water was added. Further, 0.55 g (0.0029 mol) of p-toluenesulfonyl chloride and 0.05 g (0.00022 mol) of benzyltriethylammonium chloride were added. The mixture was allowed to react at room temperature for 3 hours, and further refluxed under heat for 3 hours. After the reaction mixture was allowed to cool, the methylene chloride layer was separated and dried over sodium sulfate. The solvent was removed under reduced pressure to obtain an oil, and the oil was purified by silica gel column chromatography to give 0.40 g (0.00075 mol) of 4-methoxy-5,8-dimethyl-6-(1,3-dimethyl-5-p-toluenesulfonyloxypyrazol-4-yl)-carbonylthiochroman-1,1-dioxide (Compound 78) shown in Table 5. The yield thereof was 44%.

Table 5 shows the structures and yields of Compounds 34 to 78 obtained in the above Examples 34 to 78, and Table 6 shows the physical properties thereof.

                                      TABLE 5                                      __________________________________________________________________________                                 Prepd                                              Prep.                                                                               Starting               Compd                                                                              Structural            Yield                    Ex. No.                                                                             material               No. formula               (%)                      __________________________________________________________________________     34                                                                                   ##STR249##            34                                                                                  ##STR250##           65                       35                                                                                   ##STR251##            35                                                                                  ##STR252##           72                       36                                                                                   ##STR253##            36                                                                                  ##STR254##           53                       37                                                                                   ##STR255##            37                                                                                  ##STR256##           43                       38                                                                                   ##STR257##            38                                                                                  ##STR258##           47                       39                                                                                   ##STR259##            39                                                                                  ##STR260##           52                       40                                                                                   ##STR261##            40                                                                                  ##STR262##           78                       41                                                                                   ##STR263##            41                                                                                  ##STR264##           39                       42                                                                                   ##STR265##            42                                                                                  ##STR266##           73                       43                                                                                   ##STR267##            43                                                                                  ##STR268##           64                       44                                                                                   ##STR269##            44                                                                                  ##STR270##           40                       45                                                                                   ##STR271##            45                                                                                  ##STR272##           53                       46                                                                                   ##STR273##            46                                                                                  ##STR274##           50                       47                                                                                   ##STR275##            47                                                                                  ##STR276##           75                       48                                                                                   ##STR277##            48                                                                                  ##STR278##           54                       49                                                                                   ##STR279##            49                                                                                  ##STR280##           74                       50                                                                                   ##STR281##            50                                                                                  ##STR282##           84                       51                                                                                   ##STR283##            51                                                                                  ##STR284##           64                       52                                                                                   ##STR285##            52                                                                                  ##STR286##           77                       53                                                                                   ##STR287##            53                                                                                  ##STR288##           37                       54                                                                                   ##STR289##            54                                                                                  ##STR290##           68                       55                                                                                   ##STR291##            55                                                                                  ##STR292##           76                       56                                                                                   ##STR293##            56                                                                                  ##STR294##           25                       57                                                                                   ##STR295##            57                                                                                  ##STR296##           35                       58                                                                                   ##STR297##            58                                                                                  ##STR298##           80                       59                                                                                   ##STR299##            59                                                                                  ##STR300##           85                       60                                                                                   ##STR301##            60                                                                                  ##STR302##           100                      61                                                                                   ##STR303##            61                                                                                  ##STR304##           97                       62                                                                                   ##STR305##            62                                                                                  ##STR306##           92                       63                                                                                   ##STR307##            63                                                                                  ##STR308##           92                       64                                                                                   ##STR309##            64                                                                                  ##STR310##           28                       65                                                                                   ##STR311##            65                                                                                  ##STR312##           22                       66                                                                                   ##STR313##            66                                                                                  ##STR314##           74                       67                                                                                   ##STR315##            67                                                                                  ##STR316##           95                       68                                                                                   ##STR317##            68                                                                                  ##STR318##           82                       69                                                                                   ##STR319##            69                                                                                  ##STR320##           78                       70                                                                                   ##STR321##            70                                                                                  ##STR322##           85                       71                                                                                   ##STR323##            71                                                                                  ##STR324##           86                       72                                                                                   ##STR325##            72                                                                                  ##STR326##           71                       73                                                                                   ##STR327##            73                                                                                  ##STR328##           50                       74                                                                                   ##STR329##            74                                                                                  ##STR330##           75                       75                                                                                   ##STR331##            75                                                                                  ##STR332##           76                       76                                                                                   ##STR333##            76                                                                                  ##STR334##           87                       77                                                                                   ##STR335##            77                                                                                  ##STR336##           95                       78                                                                                   ##STR337##            78                                                                                  ##STR338##           44                       __________________________________________________________________________

                  TABLE 6                                                          ______________________________________                                         Compd Infrared absorption                                                                          Proton nuclear magnetic                                    No.   spectrum *1 (cm.sup.-1)                                                                      resonance spectrum *2 (ppm)                                ______________________________________                                         34    1630 (C═O)                                                                               1.47(3H, t)2.4˜2.9(2H, m)2.44(3H,                          2840, 2950,   s)3.1˜3.8(2H, m)3.50(3H, s)                                2990(C--H)    4.08(2H, q)4.50˜4.65(H, m)                                 2500˜3450(O--H)                                                                        5.4(H, s, broad)7.32(H, s)                                       1135, 1295,   7.57(H, d)7.92(H, d)                                             1315(SO.sub.2)                                                           35    1630(C═O) 1.47(3H, t)2.37(3H, s)                                           2830, 2950,   2.5˜3.0(2H, m)3.1˜3.9(2H, m)                         2955(C--H)    3.50(H, s)4.08(2H, q)                                            2600˜3450(O--H)                                                                        4.42˜4.60(H, m)6.7(H, s, broad)                            1135, 1295,   7.28(H, d)7.35(H, s)7.72(H, d)                                   1315(SO.sub.2)                                                           36    1640(C═O) 1.46(3H, t)2.5˜2.8(2H, m)                                  2850, 2970,   3.2˜3.9(2H, m)3.51(3H, s)                                  3010(C--H)    4.08(2H, q)4.71˜4.83(H, m)                                 2500˜3480(O--H)                                                                        5.60(H, broad)7.35(H, s)7.56(H, s)                               1140, 1325,                                                                    1340(SO.sub.2)                                                           37    1630(C═O) 1.34(3H, t)2.3˜2.7(2H, m)                                  2830, 2950,   2.36(3H, s)3.0˜3.6(2H, m)                                  2990(C--H)    3.50(3H, s)3.99(2H, q)                                           2600˜3450(O--H)                                                                        4.64˜4.80(H, m)7.53(H, s)                                  1130, 1295,   7.90(H, s)                                                       1315(SO.sub.2)                                                           38    1640(C═O) 1.83(3H, s)2.3˜3.0(2H, m)                                  2850, 2970,   3.4˜4.0(2H, m)3.52(3H, s)3.56(3H,                          3010(C--H)    s)4.79˜4.94(H, m)7.70(H, s)                                2600˜3500(O--H)                                                          1140, 1305,                                                                    1325(SO.sub.2)                                                           39    620(C═O)  1.21(3H, t)1.40(3H, t)                                           2940, 2980(C--H)                                                                             2.4˜3.1(2H, m)2.42(3H, s)                                  3200˜3500(O--H)                                                                        3.2˜3.7(2H, m)3.5˜4.0(2H, m)                         1120, 1285,   4.05(2H, q)4.79˜4.86(H, m)                                 1305(SO.sub.2)                                                                               7.38(H, s)7.59˜7.87(2H, m)                           40    1630(C═O) 1.30˜1.70(6H, m)2.36(3H, s)                                2850, 2950(C--H)                                                                             2.40˜2.75(2H, m)                                           2500˜3450(O--H)                                                                        3.2˜4.0(H, m)3.49(3H, s)4.08(2H,                           1140, 1295(SO.sub.2)                                                                         q)4.41˜4.57(H, m)6.95(H, s, broad)                                       7.25(H, d)7.30(H, d)                                       41    1630(C═O) 1.50˜1.70(3H, m)1.72(3H, s)                                2860, 2950(C--H)                                                                             2.2˜2.8(3H, m)2.27(3H, s)3.47(3H,                          2600˜3450(O--H)                                                                        s)3.64(3H, s)3.25˜3.95(H, m)                               1130, 1285,   4.40˜4.55(H, m)5.10(H, S, broad)                           1315(SO.sub.2)                                                                               7.10(H, d)                                                 42    630(C═O)  1.37˜1.55(6H, m)1.6˜1.8(H, m)                        2850, 3000(C--H)                                                                             2.24˜2.74(2H, m)2.36(3H,                                   2500˜3450(O--H)                                                                        s)3.45(3H, s)4.06(2H,                                                          q)4.47˜4.68(H, m)7.08(H, d)7.40(H,                                       s)7.87(H, s, broad)                                        43    1630(C═O) 1.18˜1.54(9H, m)1.6˜1.8(H, m)                        2890, 2950,   2.10˜2.75(2H, m)2.40(3H, s)                                2990(C--H)    3.35˜3.92(2H, m)4.08(2H, q)                                2500˜3450(O--H)                                                                        4.60˜4.73(H, m)6.40(H, s, broad)                                         7.10(H, d)7.42(H, s)                                       44    1630(C═O) 1.14˜1.50(6H, m)1.8˜2.2(H, m)                        2840, 2950,   2.55˜2.85(H, m)3.1˜3.8(H, m)                         2990(C--H)    3.48(3H, s)                                                      2500˜3200(O--H)                                                                        3.90˜4.25(2H, m)4.5˜4.9(H, m)                                      7.40˜7.83(2H, m) *2                                  45    1630(C═O) 0.93(3H, t)1.35˜1.85(2H,                                   2850, 2950,   m)1.40(3H, t)2.30˜2.95(2H,                                 3000(C--H)    m)2.43(3H, s)3.35˜3.90(4H,                                 2500˜3450(O--H)                                                                        m)4.06(2H, q)4.47˜4.87(H,                                  1130, 1300(SO.sub.2)                                                                         m)5.3(H, s, broad)7.39(H, s)                                                   7.65(H, d)7.83(H, d) *3                                    46    1630(C═O) 1.45(3H, t)1.68˜1.96(H, m)                                 2840, 2960,   2.25(3H, s)2.41(3H, s)                                           3000(C--H)    2.64˜2.93(2H, m)                                           2600˜3150(O--H)                                                                        3.10˜3.33(H, m)3.45(3H, s)                                               4.06(2H, q)4.50˜4.60(H, m)                                               7.20(H, s)7.41(H, s)7.64(H, s,                                                 broad) *2                                                  47    1630(C═O) 1.45(3H, t)2.36(3H, s)                                           2850, 2960,   2.46˜2.90(2H, m)2.75(3H, s)                                3000(C--H)    3.10˜3.90(2H, m)3.47(3H, s)                                2500˜3450(O--H)                                                                        4.09(2H, q)4.50˜4.58(H, m)                                 1130, 1300,   7.0(H, s, broad)7.28˜7.34(2H, m)                           1320(SO.sub.2)                                                                               *2                                                         48    1620(C═O) 1.45(3H, t)1.6˜1.9(H,                                      2850, 2960,   m)2.5˜3.0(2H, m)3.1˜3.4(H,                           3000(C--H)    m)3.43(3H, s)4.08(2H,                                            2600˜3100(O--H)                                                                        q)4.70˜4.80(H, m)7.30(H,                                                 dd)7.62(H, m)8.6(H, s, broad) *2                           49    1620(C═O) 1.26(3H, t)1.45(3H, t)                                           2870, 2930,   1.66˜1.96(H, m)2.24(3H, s)2.41(3H,                         2980(C--H)    s)2.62˜2.86(2H, m)3.15˜3.60(H,                       2600˜3200(O--H)                                                                        m)3.75(2H, q)4.06(2H, q)                                                       4.60˜4.72(H, m)6.85(H, s, broad)                                         7.19(H, s)7.42(H, s) *2                                    50    1630(C═O) 1.26(3H, t)1.46(3H, t)2.38(3H, s)                                2940, 2980(C--H)                                                                             2.47˜2.85(2H, m)2.77(3H, s)                                3100˜3450(O--H)                                                                        3.1˜4.0(2H, m)3.63(2H, q)4.08(2H,                          1125, 1285,   q)4.58˜4.68(H, m)6.60(H, s, broad)                         1310(SO.sub.2)                                                                               7.31(H, s)7.34(H, s)                                                           *2                                                         51    1620(C═O) 1.22(3H, t)1.45(3H, t)1.6˜2.0(H, m)                        2930, 2970(C--H)                                                                             2.4˜3.1(2H, m)3.2˜3.4(H, m)                          2400˜3300(O--H)                                                                        3.5˜3.9(2H, m)4.07(2H, q)                                                4.80˜4.90(H, m)7.30(H, dd)7.61(H,                                        d)8.2(H, s, broad)                                                             *2                                                         52    1630(C═O) 0.91(3H, t)1.20˜1.54(7H,                                   2890, 2960(C--H)                                                                             m)2.38(3H, s)2.48˜2.90(2H,                                 400˜3500(O--H)                                                                         m)2.77(3H, s)3.10˜4.15(4H,                                 1130, 1290,   m)4.08(2H, q)4.56˜4.66(H,                                  1310(SO.sub.2)                                                                               m)5.2(H, s, broad)7.28˜7.35(2H,                                          m) *2                                                      53    1620(C═O) 1.67(3H, s)2.35(3H, s)2.4˜2.7(2H,                          2930(C--H)    m)2.8˜3.8(2H, m)3.48(3H,                                   2600˜3450(O--H)                                                                        s)3.55(3H, s)4.66˜4.76(H, m)5.8(H,                         1120, 1285,   s, broad)7.50(H, d)7.83(H, d)                                    1305(SO.sub.2)                                                                               *3                                                         54    1640(C═O) 2.3˜2.7(2H, m)2.40(3H, s)                                  2960, 3000(C--H)                                                                             2.85˜3.85(2H, m)3.50(3H,                                   2600˜3500(O--H)                                                                        s)3.66(3H, s)4.67˜4.76(H, m)5.5(H,                         1135, 1295,   s, broad)7.35(H, s)7.63(H, d)7.83(H,                             1315(SO.sub.2)                                                                               d) *3                                                      55    1630(C═O) 1.12˜1.51(9H, m)2.26˜2.67(H, m)                      2940, 2980(C--H)                                                                             2.48(3H, s)2.80˜3.45(2H, m)                                2600˜3450(O--H)                                                                        3.55˜3.80(H, m)3.90˜4.0(H, m)                        1130˜1310(SO.sub.2)                                                                    4.07(2H, q)4.3(H, s, broad)                                                    5.0˜5.10(H, m)7.38(H, s)                                                 7.64(H, d)7.83(H, d) *2                                    56    1635(C═O) 1.52˜1.94(H, m)1.77(3H, s)                                 2960(C--H)    2.24(3H, s)2.30(3H, s)2.56˜2.94(2H,                        2600˜3450(O--H)                                                                        m)3.08˜3.32(H, m)3.44(3H,                                                s)3.62(3H, s)4.45˜4.55(H,                                                m)6.95(H, s)7.6(H, s, broad)                                                   *2                                                         57    1620(C═O) 1.27(3H, d)1.46(3H, t)2.39(3H, s)                                2940, 2980(C--H)                                                                             2.76(3H, s)2.84˜3.35(2H, m)                                2600˜3450(O--H)                                                                        3.43(3H, s)3.60˜3.97(H, m)                                 1150, 1290(SO.sub.2)                                                                         4.08(2H, q)4.36˜4.48(H, m)                                               6.16(H, s, broad)7.26˜7.35(2H, m)                                        *2                                                         58    1630(C═O) 1.35(3H, d)1.46(3H, t)2.44(3H, s)                                2960, 2950,   2.77(3H, s)2.83˜3.27(2H, m)                                2980(C--H)    3.46(3H, s)3.75˜3.95(H, m)                                 2400˜3250(O--H)                                                                        4.08(2H, q)4.47˜4.55(H, m)                                 1125, 1295(SO.sub.2)                                                                         6.04(H, s, broad)7.27˜7.33(2H, m)                                        *2                                                         59    1635(C═O) 1.2˜1.6(9H, m)2.1˜2.8(2H, m)                         2890, 2950,   2.37(3H, s)3.45˜4.30(3H, m)                                3000(C--H)    4.10(2H, q)4.55˜4.65(H, m)                                 3300˜3450(O-- H)                                                                       7.26˜7.74(2H, m)8.4(H, s, broad)                           1140, 1290,                                                                    1320(SO.sub.2)                                                           60    1650(C═O) 1.12˜1.47(6H, m)2.5˜3.3(2H, m)                       2960, 3000(C--H)                                                                             3.40˜3.52(3H, m)3.7˜4.0(H, m)                        2500˜3200(O--H)                                                                        4.04(2H, q)4.62˜4.85(H, m)                                 1140, 1275,   7.32˜7.87(2H, m)                                           1315(SO.sub.2)                                                           61    1640(C═O) 1.45(3H, t)2.6˜2.8(2H, m)                                  2850, 2960,   3.2˜4.0(2H, m)3.47(3H, s)4.10(2H,                          3000(C--H)    q)4.65˜4.80(H, m)7.4˜7.9(H, m)                       2600˜3450(O--H)                                                                        7.55(H, d)9.2(H, s, broad)                                       1140, 1300,                                                                    1325(SO.sub.2)                                                           62    1630(C═O) 1.23(3H, t)1.47(3H, t)2.4˜2.8(2H,                          2950, 2990(C--H)                                                                             m)3.1˜3.9(4H, m)4.10(2H, q)                                2400˜3300(O--H)                                                                        4.76˜4.90(H, m)7.1(H, s, broad)                            1130, 1320(SO.sub.2)                                                                         7.3˜7.9(H, m)7.55(H, d)                              63    1630(C═O) 1.45(3H, t)2.37(3H, s)                                           2830, 2940,   2.52˜2.80(2H, m)2.73(3H, s)                                2990(C--H)    3.18˜3.90(2H, m)3.48(3H, s)                                2600˜3450(O--H)                                                                        4.07(2H, q)4.48˜4.54(H, m)                                 1000(SO)      6.5(H, s, broad)7.31(2H, s)                                64    1660(C═O) 1.52(3H, t)2.30(3H, d)2.5˜2.9(2H,                          2960, 3000(C--H)                                                                             m)3.1˜4.0(2H, m)3.48(3H, s)                                1130, 1300(SO.sub.2)                                                                         3.62(3H, s)4.23(2H, q)                                           1200, 1400(OSO.sub.2)                                                                        4.44˜4.55(H, m)                                                          7.20(H, d)7.45(H, s) *2                                    65    1660(C═O) 1.50(3H, t)2.29(3H, s)2.47(3H, s)                                2950, 2990(C--H)                                                                             2.50˜2.70(2H, m)3.12˜3.90(2H, m)                     1140, 1300(SO.sub.2)                                                                         3.47(3H, s)4.16(2H, q)                                           1190, 1400(OSO.sub.2)                                                                        4.54˜4.64(H, m)7.00(H, d)7.36(H,                                         s)7.50(2H, d)7.82(2H, d)                                                       *2                                                         66    1665(C═O) 1.43(3H, t)2.36(3H, s)2.48(3H, s)                                2850, 2960,   2.67˜2.97(2H, m)3.35˜3.70(2H, m)                     3000(C--H)    3.53(3H, s)4.12(2H, q)                                           1140, 1300(SO.sub.2)                                                                         4.66˜4.75(H, m)7.40˜7.82(7H, m)                      1205, 1380(OSO.sub.2)                                                                        *3                                                         67    1660(C═O) 1.18(3H, t)1.50(3H, t)1.86˜2.30(2H,                        2960, 2990(C--H)                                                                             m)2.37(3H, s)2.54˜2.84(2H, m)                              1135, 1295,   3.12˜3.78(2H, m)3.48(3H,                                   1315(SO.sub.2)                                                                               s)3.65(2H, t)4.50˜4.60(H,                                  1175, 1380(OSO.sub.2)                                                                        m)7.47(H, s)7.50(H, d)7.89(H, d)                                               *2                                                         68    1660(C═O) 1.51(3H, t)2.29(3H, s)2.46(3H, s)                                2940(C--H)    2.64˜2.94(2H, m)2.69(3H, s)                                1125, 1290,   3.10˜3.90(2H, m)3.46(3H, s)                                1310(SO.sub.2)                                                                               4.20(2H, q)4.45˜4.55(H, m)                                 1180, 1390(OSO.sub.2)                                                                        7.06(H, s)7.34(H, s)7.48(2H, d)                                                7.84(2H, d) *2                                             69    1660(C═O) 1.14(3H, t)1.51(3H, t)1.66˜1.88(H,                         2850, 2970,   m)1.85˜2.20(2H, m)2.24(3H, s)                              3000(C--H)    2.35(3H, s)2.56˜2.90(2H, m)                                1185, 1395(OSO.sub.2)                                                                        3.08˜3.33(H, m)3.44(3H, s)3.60(2H,                                       t)4.21(2H, q)4.48˜4.58(H, m)                                             7.10(H, s)7.56(H, s)                                       70    1665(C═O) 1.54(3H, t)1.64˜1.93(H, m)2.15(3H,                         2850, 2970,   s)2.30(3H, s)2.60˜2.90(2H, m)                              3000(C--H)    3.12˜3.33(H, m)3.45(3H, s)                                 1205, 1400(OSO.sub.2)                                                                        4.25(2H, q)4.48˜4.58(H, m)6.92(H,                                        s)7.51(2H, d)7.60(H, s)7.85(2H, d)                         71    1665(C═O) 1.20(6H, d)1.51(3H, t)                                           2960, 2990(C--H)                                                                             2.25˜2.90(3H, m)2.31(3H, s)                                1130, 1300(SO.sub.2)                                                                         2.75(3H, s)3.10˜4.0(2H, m)                                 1185, 1385(OSO.sub.2)                                                                        3.48(3H, s)3.61(2H, d)4.22(2H, q)                                              4.45˜4.55(H, m)7.23(H, s)                                                7.49(H, s)                                                 72    1665(C═O) 1.51(3H, t)2.20˜2.95(2H, m)                                2830, 2950,   2.28(3H, s)2.68(3H, s)                                           2990(C--H)    3.10˜3.40(H, m)3.45(3H, s)                                 1130, 1290(SO.sub.2)                                                                         3.62˜4.02(H, m)4.20(2H, q)                                 1200, 1390(OSO.sub.2)                                                                        4.45˜4.55(H, m)7.07(H, s)                                                7.53˜8.01(6H, m)                                     73    1660(C═O) 1.55(3H, t)2.18(3H, s)2.40˜2.90(2H,                        2830, 2950,   m)2.70(3H, s)3.10˜3.35(H,                                  3000(C--H)    m)3.45(3H, s)3.65˜4.05(H,                                  1130, 1295(SO.sub.2)                                                                         m)4.26(2H, q)4.50˜4.60(H,                                  1200, 1400(OSO.sub.2)                                                                        m)7.03(H, s)7.43(H,                                                            s)7.57˜7.59(2H, m)7.92˜7.95(H,                                     m)                                                         74    1660(C═O) 1.17(3H, t)1.51(3H, t)1.90˜2.30(2H,                        2820, 2940,   m)2.32(3H, s)2.48˜2.90(2H, m)                              2980(C--H)    2.75(3H, s)3.12˜3.90(2H,                                   1120, 1285,   m)3.46(3H, s)4.22(2H,                                            1305(SO.sub.2)                                                                               q)4.45˜4.55(H, m)7.23(H, s)7.47(H,                         1170, 1375(OSO.sub.2)                                                                        s)                                                         75    1665(C═O) 1.53(3H, t)2.26(3H, s)2.45˜ 2.90(2H,                       2830, 2950,   m)2.71(3H, s)3.13˜3.88(2H, m)                              2990(C--H)    3.45(3H, s)4.23(2H, q)4.45˜4.55(H,                         1130, 1290,   m)7.08(H, s)7.51(H, s)7.59(2H, d)                                1310(SO.sub.2)                                                                               7.95(2H, d)                                                      1195, 1405(OSO.sub.2)                                                    76    1665(C═O) 1.53(3H, t)2.25(3H, s)2.53˜2.75(2H,                        2840, 2960,   m)2.68(3H, s)3.03˜3.35(2H, m)                              3000(C--H)    3.47(3H, s)4.24(2H, q)4.44˜4.55(H,                         1040(SO)      m)7.09(H, s)7.47(H, s)7.59(2H, d)                                1200, 1410(OSO.sub.2)                                                                        7.97(2H, d)                                                77    1630(C═O) 1.70(3H, s)2.09(3H, s)                                           2840, 2950,   2.29(3H, s)2.50˜2.90(2H, m)                                3000(C--H)    3.10˜4.0(2H, m)3.46(3H, s)                                 2600˜3450(O--H)                                                                        3.64(3H, s)4.45˜4.55(H, m)                                 1125, 1290(SO.sub.2)                                                                         7.14(H, s)8.8(H, s, broad)                                 78    1665(C═O) 2.15˜2.90(2H, m)2.27(3H, s)                                2840, 2950(C--H)                                                                             2.38(3H, s)2.46(3H, s)2.60(3H, s)                                1130, 1290(SO.)                                                                              3.15˜4.10(2H, m)4.50˜4.60(H.m)                       1190, 1400(OSO.sub.2)                                                                        3.47(3H, s)3.71(3H, s)                                                         7.04(H, s)7.42(4H, dd)                                     ______________________________________                                          *1 KBr tablet method                                                           *2 Solvent/deutero chloroform Internal standard/tetramethylsilane        

REFERENTIAL EXAMPLE

As Referential Example, the synthesis of 6-bromo-5-methylthiochroman-4-one used as the starting material in Preparation Example 1 will be described below.

Referential Example (Synthesis of 6-bromo-5-methylthiochroman-4-one)

A one-liter, three-necked flask was charged with 0 g (0.4 mol) of m-toluenethiol, 29 g (0.4 mol) of acrylic acid and 1.0 ml of triethylamine and the mixture was allowed to react at 150° C. for 1 hour. After the reaction mixture was allowed to cool, 200 ml of acetic acid was added to the reaction mixture, and the mixture was heated up to 50° C. to form a complete solution. Then, 21 ml of bromine was gradually added over 30 minutes, and the mixture was further allowed to react at 50° to 50° C. for 1 hour. After the reaction was completed, the reaction mixture was poured into 1.5 liters of a 1% sodium hydrogensulfite aqueous solution, and the formed solid was recovered by filtration and dried to give 110 g of 3-(4-bromo-3-methylphenylthio)propionic acid as a crude product.

27.5 Grams (0.1 mol) of the above-obtained crude 3-(4-bromo-3-methylphenylthio)propionic acid was charged into a one-liter, three-necked flask, and 200 ml of dichloromethane was added to form a complete solution. Then, 100 ml of concentrated sulfuric acid was added over 30 minutes, and the mixture was allowed to react for 1 hour by refluxing it under heat. After allowed to cool, the reaction mixture was poured into 1 liter of water, and the mixture was extracted with dichloromethane. The dichloromethane layer was washed with a saturated sodium bicarbonate aqueous solution, and dried over sodium sulfate. The dichloromethane was distilled off under reduced pressure, and the remainder was purified by silica gel column chromatography to give 4.4 g of 6-bromo-5-methylthiochroman-4-one. The yield thereof was 17%.

NMR (ppm, solvent CDCl₃, internal standard tetramethylsilane) 2.52 (3H,s) 2.92-3.30 (4H,m) 7.00 (H,d) 7.50 (H,d)

Herbicide Examples 1-69 and Herbicide Comparative Examples 1-4

(1) Preparation of Herbicide

97 Parts by weight of talc (trade name: Zeaklite) as a carrier, 1.5 parts by weight of alkylarylsulfonate (trade name: Neoplex, supplied by Kao-Atlas K.K.) as a surfactant and 1.5 parts by weight of a nonionic and anionic surfactant (trade name: Sorpol 800A, supplied by Toho Chemical Co., Ltd.) were uniformly pulverized and mixed to obtain a carrier for a wettable powder.

90 Parts by weight of the above carrier and 10 parts by weight of one compound of the present invention obtained in any one of the above Preparation Examples (or 10 parts by weight of pyrazolate for Herbicide Comparative Examples 1 and 3 or 10 parts by weight of the compound described in JP-A-63-122672 for Herbicide Comparative Examples 2 and 4) were uniformly pulverized and mixed to obtain a herbicide.

(2) Biological Test (Foliar treatment test, Herbicide Examples 1-45 and Comparative Examples 1 and 2)

Seeds of weeds such as crabgrass, barnyardgrass, green foxtail, cocklebur, velvetleaf and slender amaranth and seeds of corn, wheat and barley were sown in 1/5,000-are Wagner pots filled with upland soil, and covered with upland soil. Then, the seeds were grown in a greenhouse, and when they grew to plants at one or two-leaved stage, a pre-determined amount of the herbicide prepared in the above (1) was suspended in water and uniformly sprayed to foliar portions at a rate of 200 liters/10 are. Thereafter, the plants were grown in the greenhouse, and 20 days after the treatment, the herbicide was determined for herbicidal efficacy. Table 7 shows the results.

The herbicidal efficacy and the phytotoxicity to the crops are shown on the basis of the following ratings.

    ______________________________________                                                        Ratio of remaining plant                                        (Ratings)      weight to non-treated [%]                                       ______________________________________                                         Herbicidal efficacy                                                            0               81-100                                                         1              61-80                                                           2              41-60                                                           3              21-40                                                           4               1-20                                                           5              0                                                               Phytotoxicity                                                                  -              100                                                             ±           95-99                                                           +              90-94                                                           ++             80-89                                                           +++             0-79                                                           ______________________________________                                    

                  TABLE 7                                                          ______________________________________                                                        Herbicidal efficacy                                                     Com-                   Barn-                                                   pound   Dosage   Crab- yard- Green Cock-                               No.     used    [g.sup.a.i. /are]                                                                       grass glass foxtail                                                                              lebur                               ______________________________________                                         Herbicide                                                                              No. 34  10       5     5     5     5                                   Example 1        3       5     5     5     5                                   Herbicide                                                                              No. 35  10       5     5     5     5                                   Example 2        3       5     5     5     5                                   Herbicide                                                                              No. 36  10       5     5     5     5                                   Example 3        3       5     5     5     5                                   Herbicide                                                                              No. 37  10       5     5     5     5                                   Example 4        3       5     5     5     5                                   Herbicide                                                                              No. 38  10       5     5     5     5                                   Example 5        3       4     5     5     5                                   Herbicide                                                                              No. 39  10       5     5     5     5                                   Example 6        3       5     5     5     5                                   Herbicide                                                                              No. 40  10       5     5     5     5                                   Example 7        3       5     4     5     5                                   Herbicide                                                                              No. 41  10       5     5     5     5                                   Example 8        3       5     4     4     4                                   Herbicide                                                                              No. 42  10       5     5     5     5                                   Example 9       3        4     4     4     4                                   Herbicide                                                                              No. 43  10       5     5     5     5                                   Example 10       3       4     4     4     4                                   Herbicide                                                                              No. 44  10       5     4     4     4                                   Example 11      3        4     4     4     4                                   Herbicide                                                                              No. 45  10       5     5     5     5                                   Example 12      3        5     5     5     5                                   Herbicide                                                                              No. 46  10       5     5     5     5                                   Example 13       3       5     5     5     5                                   Herbicide                                                                              No. 47  10       5     5     5     5                                   Example 14       3       5     5     5     5                                   Herbicide                                                                              No. 48  10       4     5     4     4                                   Example 15       3       4     4     4     4                                   Herbicide                                                                              No. 49  10       5     5     5     5                                   Example 16       3       4     4     5     5                                   Herbicide                                                                              No. 50  10       5     5     5     5                                   Example 17       3       5     5     5     5                                   Herbicide                                                                              No. 51  10       5     5     5     5                                   Example 18       3       5     5     5     5                                   Herbicide                                                                              No. 52  10       4     4     5     4                                   Example 19       3       4     4     4     4                                   Herbicide                                                                              No. 53  10       5     5     5     5                                   Example 20       3       4     4     5     5                                   Herbicide                                                                              No. 54  10       5     5     5     5                                   Example 21       3       5     5     5     5                                   Herbicide                                                                              No. 55  10       5     5     5     5                                   Example 22       3       5     5     5     5                                   Herbicide                                                                              No. 56  10       5     5     5     5                                   Example 23       3       4     5     5     5                                   Herbicide                                                                              No. 57  10       5     5     5     5                                   Example 24       3       5     5     5     5                                   Herbicide                                                                              No. 58  10       5     5     5     5                                   Example 25       3       5     5     5     5                                   Herbicide                                                                              No. 59  10       5     5     5     5                                   Example 26       3       4     5     4     5                                   Herbicide                                                                              No. 60  10       5     5     5     5                                   Example 27       3       5     4     4     5                                   Herbicide                                                                              No. 61  10       5     5     5     5                                   Example 28       3       5     4     4     5                                   Herbicide                                                                              No. 62  10       5     5     5     5                                   Example 29       3       5     5     5     5                                   Herbicide                                                                              No. 63  10       5     5     5     5                                   Example 30       3       5     5     5     5                                   Herbicide                                                                              No. 64  10       5     5     5     5                                   Example 31       3       4     5     4     5                                   Herbicide                                                                              No. 65  10       5     5     5     5                                   Example 32       3       4     5     5     5                                   Herbicide                                                                              No. 66  10       5     5     5     5                                   Example 33       3       4     5     4     5                                   Herbicide                                                                              No. 67  10       5     5     5     5                                   Example 34       3       5     5     5     5                                   Herbicide                                                                              No. 68  10       5     5     5     5                                   Example 35       3       5     5     5     5                                   Herbicide                                                                              No. 69  10       4     4     5     5                                   Example 36       3       4     4     4     5                                   Herbicide                                                                              No. 70  10       4     4     5     5                                   Example 37       3       4     4     4     4                                   Herbicide                                                                              No. 71  10       5     5     5     5                                   Example 38       3       4     4     5     5                                   Herbicide                                                                              No. 72  10       5     5     5     5                                   Example 39       3       4     4     5     5                                   Herbicide                                                                              No. 73  10       4     4     4     5                                   Example 40       3       4     4     4     4                                   Herbicide                                                                              No. 74  10       5     5     5     5                                   Example 41       3       4     5     4     5                                   Herbicide                                                                              No. 75  10       5     5     5     5                                   Example 42       3       5     5     5     5                                   Herbicide                                                                              No. 76  10       5     5     5     5                                   Example 43       3       5     4     5     5                                   Herbicide                                                                              No. 77  10       5     5     5     5                                   Example 44       3       5     4     5     5                                   Herbicide                                                                              No. 78  10       5     5     5     5                                   Example 45       3       4     4     5     5                                   Herbicide                                                                              x       10       0     0     0     0                                   Compara-                                                                       tive                                                                           Example 1                                                                      Herbicide                                                                              y        3       0     0     0     3                                   Compara-                                                                       tive                                                                           Example 2                                                                      ______________________________________                                                 Herbicidal efficacy                                                            Velvet-                                                                               Slender       Phytotoxicity                                     No.       leaf     amaranth  Corn Wheat  Barley                                ______________________________________                                         Herbicide 5        5         --   --     --                                    Example 1 5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 2 5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 3 5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 4 5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 5 5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 6 5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 7 5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 8 5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 9 4        4         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 10                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 11                                                                               4        4         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 12                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 13                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 14                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 15                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 16                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 17                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 18                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 19                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 20                                                                               4        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 21                                                                               4        4         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 22                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 23                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 24                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 25                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 26                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 27                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 28                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 29                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 30                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 31                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 32                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 33                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 34                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 35                                                                               5        5         --   --     --                                    Herbicide 5        4         --   --     --                                    Example 36                                                                               4        4         --   --     --                                    Herbicide 5        4         --   --     --                                    Example 37                                                                               4        4         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 38                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 39                                                                               4        4         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 40                                                                               5        4         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 41                                                                               5        4         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 42                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 43                                                                               4        4         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 44                                                                               4        4         --   --     --                                    Herbicide 4        5         --   --     --                                    Example 45                                                                               4        4         --   --     --                                    Herbicide 0        1         --   --     --                                    Comparative                                                                    Example 1                                                                      Herbicide 3        2         --   --     --                                    Comparative                                                                    Example 2                                                                      ______________________________________                                          a.i. = abbreviation for active ingredient                                      ##STR339##      treatment, the herbicide was determined for herbicidal efficacy. Table 8      shows the results.

The herbicidal efficacy and the phytotoxicity to the crops are shown according to the basis described in (2) foliar treatment test.

                  TABLE 8                                                          ______________________________________                                                        Herbicidal efficacy                                                     Com-                   Barn-                                                   pound   Dosage   Crab- yard- Green Cock-                               No.     used    [g.sup.a.i. /are]                                                                       grass glass foxtail                                                                              lebur                               ______________________________________                                         Herbicide                                                                              No. 34  10       5     5     5     5                                   Example 46       3       5     4     5     4                                   Herbicide                                                                              No. 37  10       5     5     5     5                                   Example 47       3       4     5     4     4                                   Herbicide                                                                              No. 39  10       5     5     5     5                                   Example 48       3       5     5     5     5                                   Herbicide                                                                              No. 45  10       5     5     5     5                                   Example 49       3       5     4     5     5                                   Herbicide                                                                              No. 47  10       5     5     5     5                                   Example 50       3       4     5     5     5                                   Herbicide                                                                              No. 50  10       5     5     5     5                                   Example 51       3       4     5     4     5                                   Herbicide                                                                              No. 53  10       5     5     5     5                                   Example 52       3       5     5     5     5                                   Herbicide                                                                              No. 54  10       5     5     5     5                                   Example 53       3       5     5     5     4                                   Herbicide                                                                              No. 55  10       5     5     5     5                                   Example 54       3       5     5     5     5                                   Herbicide                                                                              No. 57  10       5     5     5     5                                   Example 55       3       5     5     5     5                                   Herbicide                                                                              No. 58  10       5     5     5     5                                   Example 56       3       5     5     4     4                                   Herbicide                                                                              No. 59  10       5     5     5     5                                   Example 57       3       5     4     5     5                                   Herbicide                                                                              No. 63  10       5     5     5     5                                   Example 58       3       5     5     5     4                                   Herbicide                                                                              No. 66  10       5     5     5     5                                   Example 59       3       5     5     4     4                                   Herbicide                                                                              No. 67  10       5     5     5     5                                   Example 60       3       5     5     5     5                                   Herbicide                                                                              No. 68  10       5     5     5     5                                   Example 61       3       5     5     4     4                                   Herbicide                                                                              No. 71  10       5     5     5     5                                   Example 62       3       5     5     5     4                                   Herbicide                                                                              No. 72  10       5     5     5     5                                   Example 63       3       5     5     5     5                                   Herbicide                                                                              No. 73  10       5     5     5     5                                   Example 64       3       5     5     5     4                                   Herbicide                                                                              No. 74  10       5     5     5     5                                   Example 65       3       5     5     5     5                                   Herbicide                                                                              No. 75  10       5     5     5     5                                   Example 66       3       5     5     5     5                                   Herbicide                                                                              No. 76  10       5     5     5     5                                   Example 67       3       5     5     5     5                                   Herbicide                                                                              No. 77  10       5     5     5     5                                   Example 68       3       5     5     4     4                                   Herbicide                                                                              No. 78  10       5     5     5     5                                   Example 69       3       5     5     4     4                                   Herbicide                                                                              x       10       0     0     0     0                                   Compara-                                                                       tive                                                                           Example 3                                                                      Herbicide                                                                              y        3       3     2     2     0                                   Compara-                                                                       tive                                                                           Example 4                                                                      ______________________________________                                                 Herbicidal efficacy                                                            Velvet-                                                                               Slender       Phytotoxicity                                     No.       leaf     amaranth  Corn Wheat  Barley                                ______________________________________                                         Herbicide 5        5         --   --     --                                    Example 46                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 47                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 48                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 49                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 50                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 51                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 52                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 53                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 54                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 55                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 56                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 57                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 58                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 59                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 60                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 61                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 62                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 63                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 64                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 65                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 66                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 67                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 68                                                                               5        5         --   --     --                                    Herbicide 5        5         --   --     --                                    Example 69                                                                               5        5         --   --     --                                    Herbicide 0        0         --   --     --                                    Comparative                                                                    Example 3                                                                      Herbicide 0        0         --   --     --                                    Comparative                                                                    Example 4                                                                      ______________________________________                                          a.i. = abbreviation for active ingredient                                      ##STR340##

Effects of the Invention

As detailed above, according to the present invention, there has been provided the novel pyrazole derivative which shows high selectivity to corn, wheat and barley and which is capable of controlling gramineous weeds and broad-leaved weeds together at a low dosage, the process for the production of the above novel pyrazole derivative, the herbicide containing the above novel pyrazole derivative as an active ingredient, and the novel intermediate compound suitable for the production of the above novel pyrazole derivative. 

What is claimed is:
 1. A pyrazole compound of the formula (I), ##STR341## wherein R¹ is a C₁ -C₆ alkyl group,each of R², R³, R⁴ and R⁵ is independently hydrogen or a C₁ -C₄ alkyl group, R⁶ is a C₁ -C₄ alkyl group, R⁷ is hydrogen or a C₁ -C₄ alkyl group, X¹ is a C₁ -C₄ alkyl group or a halogen atom, n is an integer of 1 to 3, p¹ is an integer of 0 to 2, and Q¹ is hydrogen, --SO₂ --R⁸ or ##STR342## in which R⁸ is a C₁ -C₆ alkyl group, Y is hydrogen, a C₁ -C₄ alkyl group or a halogen atom, and m¹ is an integer of 1 to 3, or a salt thereof.
 2. The pyrazole compound or the salt thereof according to claim 1, wherein in the formula (I), p¹ is
 2. 3. The pyrazole compound or the salt thereof according to claim 1, wherein in the formula (I), n is 1 and one X¹ bonds to the 5-position of a thiochroman ring.
 4. The pyrazole compound or the salt thereof according to claim 1, wherein in the formula (I), n is 2 and two X¹ s respectively bond to the 5- and 8-positions of a thiochroman ring.
 5. The pyrazole compound or the salt thereof according to claim 1, wherein each of R¹, R², R³ and R⁴ is hydrogen.
 6. The pyrazole compound or the salt thereof according to claim 1, wherein Q¹ is hydrogen, --SO₂ --R⁸ or ##STR343## in which R⁸ is a C₁ -C₆ alkyl group, Y is hydrogen, a C₁ -C₄ alkyl group or a halogen atom, and m² is 1 or
 2. 7. A herbicide composition comprising an effective herbicidal amount of the pyrazole compound of the formula (I) or the salt thereof as recited in claim 1 as an active ingredient and a carrier. 